The effects of interleukin 1 (IL-1) on glucose-induced insulin secretion from isolated rat islets of Langerhans have been examined. IL-1 both inhibits and stimulates glucose-induced insulin secretion depending on the experimental design. Inhibition of glucose-induced insulin secretion was observed after a 15-h treatment of islets with either purified IL-1, murine recombinant IL-1 (rIL-1), or human rIL-1. rIL-1 inhibition of glucose-induced insulin secretion was dose dependent with half-maximal inhibition observed at 25 pM human rIL-1. Basal insulin secretion was not affected by rIL-1 treatment. Mannose- and leucine-induced insulin secretion was also inhibited by a 15-h treatment with human rIL-1. Islets treated 15 h with inhibitory concentrations of murine IL-1 were morphologically intact, well granulated, and retained normal concentrations of insulin compared with control islets. Furthermore, human rIL-1 treatment did not affect the islet plasma membrane permeability as assessed by the measurement of the islet intracellular volume. Finally, the viability of islets treated 15 h with murine IL-1 was demonstrated by the observation that the inhibitory effects of murine rIL-1 on glucose-induced insulin secretion were reversible. In addition to the inhibitory effects of IL-1 on glucose-induced insulin secretion, purified IL-1 and human rIL-1 had stimulatory effects on glucose-induced insulin secretion under the following conditions: 1) a 90-min incubation with purified IL-1 (10% vol/vol) or in the presence of human rIL-1 (1400 pM) or 2) a 15-h incubation with relatively low concentrations of human rIL-1 (0.5 or 5 pM). In conclusion, IL-1 has complex dual effects on glucose-induced insulin secretion that include both stimulation and inhibition and depend on IL-1 concentration and time of incubation. These studies suggest that IL-1 may have a physiological role as a potent modulator of insulin secretion by islets of Langerhans.