SUMMARY.—The responses to topical application of tetrahydrofurfuryl nicotinate (Trafuril) cream were studied using a continuous skin perfusion method in clinically uninvolved skin of patients with chronic urticaria and in control patients. Trafuril causes inflammation but also renders the skin susceptible to dermographism.In non‐urticarial subjects little pharmacological activity was detected during Trafuril inflammation or after stroking the skin to induce dermographism. This suggests that Trafuril causes inflammation by a direct effect on the cutaneous vasculature. By contrast in urticarial patients histamine was recovered more frequently than in non‐urticarial patients during Trafuril inflammation, both before and after the skin was stroked. Perfusates from urticarial subjects also contained unidentified smooth muscle contracting activity which was not due to histamine, kinins, serotonin or acetyl choline. These results suggest that the skin of patients with chronic urticaria releases histamine and some other pharmacological agents more readily than that of normal subjects in response to inflammation producing st