Cell-mediated and humoral immune responses of streptozotocin-induced diabetic mice were evaluated using in vivo and in vitro immunological assays. C57BL/6 mice were rendered diabetic by a single intraperitoneal injection of 125-200 mg/kg of streptozotocin. Immunological studies were performed after the mice were diabetic (mean +/- SEM serum glucose 537 +/- 14 mg/dl) for a minimum of 4 weeks. Spleen cells from streptozotocin-induced diabetic mice exhibited significantly diminished direct IgM plaque-forming cell (PFC) responses following either in vivo or in vitro immunization with sheep erythrocytes, markedly impaired cytotoxic cell responses following in vivo or in vitro allogeneic stimulation, and diminished blastogenic response to the T-cell mitogens phytohemagglutinin and concanavalin A. In contrast the blastogenic response of diabetic spleen cells to lipopolysaccharide, a B-cell mitogen, was normal. The defects in in vivo PFC responses and in vivo cytotoxic cell responses were corrected by islet cell transplantation, suggesting that the abnormalities in immunological function of streptozotocin-induced diabetic mice are a consequence of the diabetic state and not of direct streptozotocin toxicity to lymphoid cells.