Populations of the Lost River sucker Deltistes luxatus have declined so precipitously in the Upper Klamath Basin of Oregon and California that this fish was recently listed for federal protection as an endangered species. Although Upper Klamath Lake is a major refuge for this species, fish in the lake occasionally experience mass mortalities during summer and early fall. This field study was implemented to determine if fish mortalities resulted from degraded water quality conditions associated with seasonal blooms of phytoplankton, especially Aphanizomenon flos-aquae. Our results indicated that fish mortality did not always increase as water temperature, pH, and un-ionized ammonia concentration increased in Upper Klamath Lake. Little or no mortality occurred when these water quality variables attained their maximum values. On the other hand, an inverse relation existed between fish mortality and dissolved oxygen concentration. High mortality (>90%) occurred whenever dissolved oxygen concentrations decreased to 1.05 mg/L, whereas mortality was usually low (< 10%) when dissolved oxygen concentrations equaled or exceeded 1.58 mg/L. Stepwise logistic regression also indicated that the minimum concentration of dissolved oxygen measured was the single most important determinant of fish mortality.