Significant, (P less than 0.05) inhibition of histamine induced cutaneous weal and flare reactions by ranitidine at 10(-5) M concentration has been demonstrated in a double blind, in vivo study; the results support the evidence for cutaneous H2-histamine receptors provided by previous studies using cimetidine and metiamide. The degree of inhibition of histamine mediated cutaneous reactions achieved by clemastine was increased by the administration of clemastine and ranitidine together, for ranitidine concentrations 10(-5) M (P less than 0.001) and 10(-6) M (P less than 0.05). The magnitude of the inhibitory effect of ranitidine, both administered alone and in combination with clemastine, suggests that in the production of histamine induced cutaneous weal and flare reactions, the contribution afforded by stimulation of cutaneous H2-histamine receptors is only small.