Interleukin-1 (IL-1) may be one of the effector molecules involved in the destruction of the pancreatic islet B cells resulting in insulin-dependent diabetes mellitus. Isolated islets exposed to IL-1 show an acutely increased substrate metabolism and insulin release, which is followed by a metabolic and functional suppression. Since an increased cellular uptake of calcium in the islets may be associated with both nutrient-induced insulin release and cell damage, the effects of recombinant IL-1β (rIL-β) on net cellular calcium uptake by isolated rat pancreatic islets were investigated. In short-term experiments the islets were exposed to 25 U/ml rIL-1β for 120 min in the presence of 1.7 mM or 16.7 mM glucose, or 16.7 mM glucose plus 5 mM verapamil. In these experiments rIL-1β induced an increase both in net cellular uptake of calcium and in insulin release only in the presence of 16.7 mM glucose. The stimulatory effect of rIL-1β at 16.7 mM glucose was blocked by verapamil. By long-term experiments, under tissue culture conditions in the presence of 11.1 mM glucose, islet net calcium uptake, insulin release and glucose oxidation were measured at different time points over a 24-h period. During the first 2 h of incubation 25 U/ml rIL-1β effected a significant increase of net calcium uptake, insulin release and glucose oxidation. However, after 4 – 5 h of incubation with the cytokine no such stimulatory effects were seen. After longer incubations with rIL-1β all the islet functions studied were suppressed. To further elucidate the potential role of cellular calcium uptake via voltage-dependent channels for the long-term deleterious effects of rIL-1β on islet function, isolated islets were incubated for 24 h with 25 U/ml rIL-1β in the absence and presence of 5 mM verapamil. Except for a partial protection against a decrease in islet DNA content, there was no effect of verapamil on the suppressive action of the cytokine on islet insulin content, insulin release, glucose oxidation or proinsulin-insulin and total protein biosynthesis. The combined data suggest that rIL-1β acutely increases insulin release by an increased substrate metabolism and cellular calcium uptake via voltage-dependent channels. In the suppressive phase of rIL-1β action on the pancreatic islet B cells, calcium uptake and insulin biosynthesis and release are apparently decreased by a deprived substrate metabolism.