The aim of the present study was to evaluate the effect of vasoactive intestinal peptide (VIP) on the expression and activity of receptors for the Fc portion of IgG (Fc gamma R) in human neutrophils. Cells were assayed under basal conditions and following in vitro stimulation with interferon gamma (IFN gamma). Antibody dependent-cellular cytotoxicity (ADCC) was chosen as a means of evaluating Fc gamma R activity. The results indicated that incubation with VIP (10(-6) M) during 18 h slightly diminished cytotoxicity of non stimulated neutrophils. In contrast, VIP exerted a marked inhibitory effect on neutrophils activated with IFN gamma. Similar results were obtained with forskolin, another agent that increases intracellular cAMP. Finally, using monoclonal antibodies and flow cytometry analysis, we found decreased membrane expression of Fc gamma R after VIP incubation. Taken together, these results show that VIP is able to act on human neutrophils, partially blocking IFN gamma-activation of Fc gamma R mediated functions. Modulation of neutrophil cytotoxic response by VIP may have an important role in limiting tissue injury during inflammation.