We previously reported that exogenous histamine inhibitsin vivohistamine release and eosinophil accmulation in ragweed‐challenged skin sites of sensitive human subjectes. The mechanism(s) involved were unclear. In this study, we repeated similar approaches in of the same subjects pretreated for 3 days with cimetidine, an H2receptor antagonist. The pattern of exogenous histamine effects was now different in that local exogenous histamine (50 ug/ml) did not significantly alter ragweed‐induced mast cell alteration, histamine release, or the degree of eosinophil accumulation in skin challenge sites. These findings suggest that the observed exogenous histamine inhibitory effects may be mediated through the H2recep