Reproduction of Megalonaias nervosa (Rafinesque, 1820) has not been documented for over 20 y in much of the Cumberland River, where water temperatures have decreased and flow regimes have been greatly altered by hypolimnetic discharges from impoundments. Studies in other streams have implicated low temperatures or changes in discharge patterns as causative factors inhibiting reproduction. Megalonaias nervosa were collected from the Cumberland River, translocated to the Tennessee River, and held in an embayment of Kentucky Lake. After the first and second y, samples of M. nervosa were taken from the Cumberland River, an existing population in Kentucky Lake, and the translocated group. Histological examination indicated that translocated mussels had a high incidence of hermaphroditism, and like mussels originating in Kentucky Lake, had undergone an otherwise normal reproductive development. Individuals functioning successfully as females from the translocated group had mature glochidia in their marsupia. Females from the Kentucky Lake sample also had mature glochidia present. In contrast, there was no indication of reproductive activity in gonads or marsupia of individuals collected from the Cumberland River. Our results indicate that a return to a more natural temperature regime in the Cumberland River would reinstate a normal reproductive cycle. We suspect that the altered temperature regime is also disrupting the gametogenic cycle of all mussels, including at least six federally listed endangered species occurring in the Cumberland River. These relic populations will disappear unless they are translocated or the thermal regime returned to normal.