Recent evidence supports the viewpoint that vasopressin, a neurohypophyseal peptide, should be also considered as a neuroendocrine modulator of immune and inflammatory responses. In this work we investigated the role of vasopressin in the regulation of prostaglandin E2 synthesis by human dermal fibroblasts. Recombinant human interleukin-1β increased prostaglandin E2 synthesis in fibroblasts about sixfold. The prostaglandin E2 response to interleukin-1β was attenuated by lower concentrations of vasopressin (10-10-10-9 M). By contrast, higher concentrations (10-8-10-7 M) of vasopressin effected significant enhancement of the interleukin-1β-induced prostaglandin E2 synthesis. In a similar way, vasopressin (10 -8-10-7 M), in the absence of interleukin-1, significantly increased prostaglandin E2 production. An inhibitory effect of lower concentrations of vasopressin was also observed on basal production of prostaglandin E2. The effects of vasopressin on basal and interleukin-1β-induced prostaglandin E2 synthesis were antagonized by selective vasopressin receptor antagonists. The findings presented here disclose a novel modulatory role of vasopressin on prostaglandin E2 synthesis in human dermal fibroblasts and suggest a possible role of vasopressin in the regulation of inflammation.