A wasting disease that kills rockfish and can cause a severe skin infection in humans has spread to nearly three-quarters of the rockfish in the Chesapeake Bay, cradle of the mid-Atlantic's most popular game fish.

The mycobacteriosis epidemic could carry profound implications for the rockfish, also known as striped bass. The fish fuel a $300 million industry in Maryland and Virginia, but because the bacteria kill slowly, effects on the stock are only now emerging.

But as the number of rockfish surged, the fish remained in a body of water too polluted to support the level of life it once did. That made them vulnerable to a malady researchers did not see coming -- a signal, some scientists say, that controlling fish harvests is no longer enough to ensure long-term survival of a species.

"We used to think that if you got hold of fishing, all your problems would be solved," said James H. Uphoff Jr., a biologist at the Maryland Department of Natural Resources. "But now all these ecological problems crop up, and we don't understand them."

Indeed, nearly a decade after mycobacteriosis first appeared, scientists remain utterly baffled about its implications, including those for humans. Researchers know that the Chesapeake, where most rockfish spawn, also breeds the bacterium and is the epicenter of the disease. Yet they don't know how or why it appeared, whether it will spread to other species or if the infection it causes is always fatal.

A new study suggests that since the illness was discovered among bay rockfish, non-fishing mortality among them has tripled in the upper bay. But scientists cannot explain why, at the same time, anglers are catching plenty of fish.

In humans who touch the fish, the microbe can cause a skin infection known as fish handler's disease, which is not life-threatening but can lead to arthritis-like joint problems if untreated. Watermen say the only sick fish they see are in small, overcrowded rivers and streams. The netting season that ended Feb. 28 "was a super-good season as far as catching, and a good season as far as the price," said Larry Simns, president of the Maryland Watermen's Association. With no evidence of health risk from eating the fish, watermen say, prices have remained stable.

But at Ristorante Tosca in downtown Washington, "some people ask, 'Is it safe?' " chef Massimo Fabbri said of the rockfish on the menu. Such questions have prompted Fabbri to buy the restaurant's wild rockfish from Northern Europe and Ecuador, paying about three times what he would for local bass. "Wouldn't you?" he asked.

As researchers test a long list of hypotheses, they say their search for the bacterium's source and implications highlights the limitations of modern science when pitted against the complexities of the wild.

"Scientists attempt to unravel things [and] are supposed to follow the information wherever it leads us," said Victor Crecco of the Connecticut Department of Environmental Protection, author of the mortality study. "We're going to have to do more work to explain these contradictions."

For centuries, striped bass fishing has been as rich in lore as it was in quality. In ideal conditions, rockfish can live up to 30 years: The biggest on record was a 125-pound female, landed off North Carolina in 1891. In this region, charter boat operators tell of swimsuit-wearing amateurs landing dozens of the silver-scaled fighters in a day -- the fish longer than one's arm, bellies made fat on the teeming schools of menhaden that are a chief food source.

Most rockfish begin their lives in the rivers feeding the bay. When they are 3 to 6 years old, they begin their journeys to the Atlantic Ocean, where they range as far north as Canada. At spawning time, most return to their birthplace.

This vast migration route confounds scientists' efforts to track the infection. In 1997, mycobacteriosis was discovered in adult fish, but the disease was already advanced. To find out when fish become infected, researchers such as Mark Matsche of the Maryland DNR visit rockfish spawning grounds in the upper bay and the Choptank and Potomac rivers, collecting eggs and young.

"The fish are exposed to the bacteria right from the start. . . . It's ubiquitous," he found. "It can survive in water or sediment or mucus."

An infected rockfish can appear outwardly healthy. But inside, the bacteria settle first in its spleen. The creature builds walls of scar tissue in fighting it, but the infection spreads to other organs. The rockfish loses weight, even as its insides swell, and it often develops sores. At some point -- researchers do not know exactly when -- it dies.

In the bay, "by age 1, 11 percent are infected. By age 2, it's 19 percent," Matsche said. But he cannot go beyond that -- by the third year, some fish have left the bay for open water. There is no way to see the infection's progress without dissecting the fish.

"We can't even say they die for sure," Matsche said. "The severely infected fish I catch . . . a lot of them die. Some moderately infected ones have some sign of healing going on. But I'm not able to see that same fish a year down the line."

About the same time the first diseased fish appeared, some researchers grew concerned about a possible link to fish handler's disease. In Maryland, 18 cases of the skin condition were reported in 2000. In 2004, there were 46.

The Mycobacteria strain that causes the skin disease has been found only in a small percentage of diseased fish.

Michele M. Monti, director of the Waterborne Hazards Control Program at the Virginia Department of Health, said the fish handler's bacterium can also lead to other problems, including swollen lymph glands or lung disease.

Tracking the potential effect on humans is more difficult because the states do not require that the disease be reported. So, Monti said, the low number of cases "could either be because there's not a lot of it out there . . . or they haven't gotten it diagnosed."

In the mid-1980s, rockfish numbers were so decimated by overfishing that Atlantic coastal states imposed a moratorium. Populations surged, and by 1995 the fishing ban ended. Wildlife officials call the restoration a rare triumph amid the pollution, overfishing and disease that threaten blue crabs, oysters and other species. But less than two years after victory was declared, the first diseased rockfish landed on bay shores.

James E. Price of the Chesapeake Bay Ecological Foundation said studies show that declines in the amount of menhaden in the rockfish diet coincide with the appearance of the disease. "It's logical," he said, "but nobody has any way to connect it."

Every day, as he has done for eight years, Wolfgang K. Vogelbein is surrounded by rockfish, some healthy, some dying -- he's not always sure which. Vogelbein, a fish pathologist at the Virginia Institute of Marine Science, was the first to diagnose mycobacteriosis in the bay's rockfish and determined that three-quarters of them carry it.

Last fall, Vogelbein, fish pathologist David Gauthier and mathematician John Hoenig affixed plastic tags to the bodies of 2,000 rockfish in the Rappahannock River, some outwardly diseased and some apparently healthy, with notes offering a reward for their return. They've gotten 120 from anglers. Using mathematical models, they hope to show whether the disease actually kills bay fish and estimate how long that takes.

So far, Vogelbein's team has found 10 strains of the bacteria in diseased rockfish, including two so new that their effect on humans is unknown.

"It's a difficult process trying to figure out the role of disease in a population of wild animals in a huge system like the bay," he said. "In this case, we still don't have the tools to efficiently answer the more compelling questions.

"That's just the nature of the beast."