The insulin release and insulin content of newborn rat islets incubated without or with interleukin-1 and/or hydro-cortisone were measured. Interleukin-1 (500 ng/L) induced a decrease of insulin release during day 1-3, but a partial recovery from the inhibition during day 4-7. The insulin content of the islets was not changed significantly. Hydro-cortisone had an inhibitory effect on insulin release (at 10-7M) or both insulin release and insulin content of islets (at 10-6 M). Both 10-7M and 10-6M hydrocortisone seemed to prevent the initial decrease in insulin release induced by interleukin-1 (500 ng/L) during day 1-3, but thereafter resulted in an even more marked decrease of insulin release corresponding to 51% (at10-7M) or 25% (at 10-6M) of control islets, respectively, during day 4-7. The rebound of the insulin release after interleukin-1 was not seen. Insulin content of islets was dramatically reduced to only 21% (at 10-7M) or 10% (at 10-6M) of control islets, respectively, after seven days. These results showed a marked synergism between interleukin-1 and both a near-physiological and a pharmacological dose of hydrocortisone on the inhibition of the beta-cell function of newborn rat pancreatic islets in culture.