A double-blind, randomized, placebo-controlled comparison of the analgesic and antihistaminic effects of four commonly used antihistamines (terfenadine, antazoline, diphenhydramine and cimetidine) was performed. Wheal and flare areas after histamine skin prick and sensory and pain thresholds induced by cutaneous argon laser irradiation were determined. Terfenadine, antazoline and diphenhydramine significantly reduced wheal and flare after histamine skin pricks. Only diphenhydramine increased the pain threshold to noxious cutaneous laser stimulations (22%) with a concomitant reduction of histamine wheal (61.5%) and flare (52.8%). The sensory threshold was not affected significantly. The antihistaminic and analgesic effects were not related.