In 1966‐67, 1970, and 1973‐76, New York State’s muskellunge (Esox masquinongy) hatchery, located on Chautauqua Lake, sustained total or near total losses of muskellunge fry at or near the swim‐up stage of development. Eggs incubated at the Chautauqua Hatchery and transferred to other stations resulted in swimming fish, but those held at Chautauqua did not. The chemistry of lake and well water at the muskellunge hatchery showed no departures from normal. During the production seasons of 1974 through 1976 the hatchery was operated on a controlled, experimental basis in an attempt to determine the cause of the fry losses. Fry die‐offs could be correlated with neither the physical or chemical properties of the water nor with the presence of a fish pathogenic virus or pathological tissue changes. Controlled laboratory experiments strongly implicated bacteria as the agents responsible for the muskellunge fry losses. Organisms recovered included predominately Pseudomonas sp., although Aeromonas hydrophila was also isolated; both are well‐known fish pathogens. Ultraviolet treatment of lake and well water supplies during incubation and yolk absorption resulted in effective control of fry losses.