The effects of dexamethasone on the modulation of insulin secretion by recombinant human interleukin-1 beta (IL-1) were examined in HIT-T 15 cells. The addition of IL-1 from 1.2 x 10(-8) to 10(-10) M increased insulin secretion in the 0-4-h period after IL-1 administration and prostaglandin E2 (PGE2) production was suppressed by IL-1 from 1.2 x 10(-8) to 10(-12) M. At all doses used, IL-1 inhibited insulin secretion in the 4-24-h period after IL-1 administration and PGE2 levels were increased in the culture medium. In the second experiment, the addition of 10(-7) M dexamethasone prevented the inhibitory effects of IL-1 on insulin secretion. In the third experiment, dexamethasone at 10(-7) M attenuated both the short-term stimulation of insulin release and the long-term suppression of insulin release caused by IL-1. It also prevented the effects of IL-1 on PGE2 production. The present studies suggest that dexamethasone may have a suppressive action on the effects of IL-1 on in vitro insulin secretion.