Evidence is accumulating that adrenal steroids may be involved in the metabolic effects of cytokines. We evaluated the possible involvement of glucocorticoids in the inhibition of pancreatic insulin secretion by interleukin-1 beta (IL-1 beta), one of the cytokines produced by inflammatory cells. In the first group of experiments, adrenalectomized rats showed a significant reduction in basal and glucose (0.5 g/kg, i.v.)-stimulated immunoreactive insulin (IRI) levels after injection of IL-1 beta (1.0 microgram/kg), but intact rats did not. Pretreatment with IL-1 beta increased plasma glucose levels 2 and 15 min after an i.v. bolus of glucose in adrenalectomized rats. In the second group of experiments, dexamethasone supplement (0.1 mg/kg) given to adrenalectomized rats cancelled the reduction in plasma glucose levels by IL-1 beta, and rats treated with 1.0 mg dexamethasone/kg showed a significant increase in basal IRI levels and enhanced serum IRI levels after IL-1 beta injection. However, 1.0 mg deoxycorticosterone/kg given daily for 7 days failed to cancel the effect of IL-1 beta on the reduction of serum IRI levels, although it attenuated the weight loss after adrenalectomy. The data suggested that withdrawal of glucocorticoids after adrenalectomy potentiates the effect of IL-1 beta on the reduction of serum IRI levels. Glucocorticoids may have a protective action against the reduction of serum IRI levels by IL-1 beta.