Interleukin-1 beta (IL-1 beta) has been shown by several investigators to be a stimulator of adrenal glucocorticoid production in vivo. However, little evidence exists for direct actions of IL-1 beta on the adrenal gland. We sought to elucidate the direct effects, if any, of IL-1 beta on human fetal adrenal steroidogenesis in the presence and absence of ACTH in both cell and organ cultures. We studied the effects of several doses of recombinant human IL-1 beta (0.05, 0.5, and 5 U/ml), in the presence and absence of two doses of ACTH (0.1 and 1 microgram/ml). With all doses of IL-1 beta, we were unable to demonstrate alterations in basal adrenal steroidogenesis as measured by dehydroepiandrosterone sulfate and cortisol production. Whereas both doses of ACTH induced significant increases in steroid production over control values (P less than 0.05), there was no additional effect on steroidogenesis when IL-1 beta was added to cultures containing ACTH. We conclude that although IL-1 beta may act in conjunction with other products of the immune system to modulate adrenal cortisol production, IL-1 beta alone does not directly influence human fetal adrenal steroidogenesis. Rather, it is likely that this cytokine acts via stimulation of pituitary ACTH production.