Inflammation and infection induce an acute phase response. The response is characterized by fever and production of interleukin-1 (IL-1). In the present study we evaluated the effects of interleukin-1 on Leydig cell function in primary culture. hCG-stimulated testosterone formation was markedly reduced by IL-1, with an ED50 of 1 U/ml. Basal testosterone production was slightly enhanced in the presence of low concentrations of IL-1, while high concentrations of IL-1 inhibited testosterone formation. Significant inhibition of hCG-stimulated testosterone formation was noted as early as 8 h after the addition of IL-1. IL-1 also inhibited hCG-stimulated cAMP formation, as well as 8-bromo-cAMP- and forskolin-stimulated testosterone synthesis. Furthermore, LH binding to Leydig cells was reduced by human IL-1. The inhibitory effects of IL-1 were reversed only partially by the addition of a cyclooxygenase inhibitor, indomethacin (0.1 mM), even though prostaglandin E2 formation was completely blocked. This indicates that the observed effects of IL-1 are not completely mediated by increased PGE2 formation. The present study suggests that IL-1 is a potent modulator of Leydig cell steroidogenesis. Decreased testosterone formation may modulate the immune response and contribute to the catabolic changes occurring during infection.