The suppressive and cytotoxic effects of interleukin-1 beta (IL-1 beta) on rodent insulin-producing cells observed in vitro are probably mediated through formation of nitric oxide (NO). In this study we demonstrate that IL-1-induced NO formation in isolated rat islets and insulin-producing HIT cells is more sensitive to inhibition by NG-monomethyl-L-arginine than to inhibition by NG-nitro-L-arginine, thus suggesting that IL-1-exposed insulin-producing cells express an isoform of nitric oxide synthase similar to that present in activated macrophages. Furthermore, IL-1 beta markedly increased the mRNA levels of the inducible macrophage form of nitric oxide synthase in HIT cells.