A simple way to study a histamine antagonist in man is to observe the effect it has on the magnitude of the skin reaction to intradermal histamine. The aim of the present study was to evaluate the antihistamine activity of single oral doses of 75 mg cinnarizine using 75 mg diphenhydramine as control, both being compared to placebo. The study was performed with two groups of 5 healthy subjects, each group receiving one of the active treatments or placebo randomly under blind conditions. All subjects received intradermal injections on the forearm of a 0.05 ml saline solution containing 5 micrograms of histamine before and at different times after drug intake. The histamine-induced wheal area was measured and, after drug administration, the percent decrease of the wheal area was calculated. Results showed that diphenhydramine produced a significant inhibition of the histamine-induced wheal size at 1.5 h which lasted up to 4 h after drug administration, reaching maximum inhibition at 2.5 h. After cinnarizine treatment no significant decrease of the histamine-induced wheal area was observed at any time.