The effects of cytokines in stimulating neurohypophysial hormone release have not been well characterized. In the present study, we have investigated the effect of intraperitoneal injection of recombinant human interleukin (IL)-1β on oxytocin release in sham-operated controls, adrenalectomized (ADX) rats and ADX rats given either low or high doses of the synthesis glucocorticoid dexamethasone. In a second study, we determined the effect of central injection of IL-1β on both oxytocin and arginine vasopressin (AVP) release in sham-operated and ADX rats. We were unable to demonstrate an increase in plasma oxytocin in intact rats in response to intraperitoneal injection of IL-1β. In contrast, we found a substantial and sustained increase in plasma oxytocin concentrations in ADX rats. This stimulation was abolished by treatment with dexamethasone at both the low and high doses. Following central injection of IL-1β, we were unable to demonstrate any increase in either oxytocin or AVP, despite the ability of this dose of cytokine to stimulate the hypothalamo-pituitary-adrenal axis, as evidenced by increased circulating corticosterone. It appears that circulating glucocorticoids may exert a tonic inhibitory effect on the release of oxytocin in response to peripheral stimulation by IL-1β.