Itching is a well known side-effect of opiate therapy. To gain insight into the possible contribution of opiate receptors to itching we compared the antipruritic effect of naltrexone (Nemexin), an opiate antagonist, to an H1-receptor antagonist and to placebo. In a double blind cross-over study on 15 healthy volunteers, 25 mg naltrexone or placebo was orally given 60 min prior to a histamine stimulus. In a second, otherwise identical experiment, 10 mg cetirizine, an H1 blocker, or placebo was orally given 12 h before the experiment to the same group of volunteers. Histamine was applied iontophoretically to the forearm skin and the following parameters were assessed thereafter: weal and flare size, itch intensity and the extension of the area of alloknesis ('itchy skin') around the application site. Naltrexone had no effect on the vascular histamine reactions 'weal' and 'flare', whereas cetirizine abolished the weal reactions and greatly diminished the flare reactions. Both naltrexone and cetirizine significantly diminished histamine induced itching. In contrast to placebo and cetirizine, naltrexone abolished alloknesis completely in four of 15 volunteers and in the others alloknesis was greatly reduced after naltrexone. Since vascular reactions to histamine are of peripheral origin, whereas alloknesis depends on central nervous mechanisms, our findings suggest a pronounced centrally mediated action of naltrexone on histamine induced pruritus.