To determine the importance of adrenal steroid in the effects of interleukin-1, we investigated changes in the number of islet cells reactive toward antiserum to insulin (anti-Ins) by intraperitoneal administration of recombinant human interleukin-1 beta (IL-1) in intact and adrenalectomized (ADX) rats. IL-1 significantly reduced serum insulin levels in ADX rats only, while it similarly decreased plasma glucose levels. In intact rats, IL-1 did not affect the number of islet cells reactive to anti-Ins, although cytoplasmic immunostaining tended to be reduced by IL-1 treatment. Only adrenalectomy decreased the number of islet cells immunostained by anti-Ins. Furthermore, IL-1 treatment significantly reduced the number of islet cells reactive to anti-Ins in ADX rats. The present study immunohistochemically supported our working hypothesis that the withdrawal of adrenal steroids by adrenalectomy enhances the islet cell sensitivity to exogenous administration of IL-1.