Survivorship of zebrafish, Danio rerio, was measured during lethal hypoxic stress after pretreatment in water at either ambient oxygen or at a lowered, but nonlethal, level of oxygen. Acclimation to nonlethal hypoxia (pO2 @ 15 Torr; ca. 10% air-saturation) for 48 hr significantly extended survival time during more severe hypoxia (pO2 @ 8 Torr; ca. 5% air-saturation) compared to survival of individuals with no prior hypoxic exposure. The magnitude of the acclimation effect depended upon the sex of the fish: hypoxia pretreatment increased the survival times of males by a factor of approximately 9 and that of females by a factor of 3 relative to controls. In addition, survival time of control and hypoxia acclimated fish depended upon when in the year experiments were conducted. Survival times were 2–3 times longer when measured in the late fall or winter compared to survival times measured during the spring or summer. These results demonstrate a direct survival benefit of short-term acclimation to hypoxia in this genetically tractable fish. The fact that the acclimation effect depended upon the sex of the fish and the season during which experiments were conducted demonstrates that other genetic and/or environmental factors affect hypoxia tolerance in this species