OBJECTIVE: To investigate the relaxant action of histamine on human corpus cavernosum in vitro and the erectile response caused by the intracavernous injection of histamine in patients with psychogenic impotence. PATIENTS AND METHODS: Human corpus cavernosum (HCC) tissue was cut into strips of approximately 2 cm and suspended in a cascade bioassay. The strips were then superfused with oxygenated and warmed Krebs solution and precontracted with noradrenaline (3 microM). Glyceryl trinitrate, acetylcholine and histamine were injected as a single bolus in the absence or in the presence of mepyramine and cimetidine. For the in vivo studies, histamine (30-60 micrograms) was injected intracavernously as a single bolus into the right corpus cavernosum 1 cm from the balamo-preputial sulcus. Similar protocols were carried out for papaverine (50 mg). The erectile response was divided into four grades: no response, tumescence, partial and full erection. RESULTS: In vitro studies demonstrated that histamine (3-100 micrograms) caused dose-dependent relaxation of the HCC strips which was significantly inhibited by cimetidine (5-10 microM). The histamine H1 receptor antagonist mepyramine (1 microM) potentiated histamine-induced relaxation. The co-infusion of both mepyramine and cimetidine did not abolish histamine-induced relaxation. When injected intracavernously in humans, histamine (30 micrograms) caused full erection in 13% of the patients, whereas 87% had partial erection or tumescence. A higher dose of histamine (60 micrograms) caused full erection in 26% of the patients and 74% had partial erection or tumescence. Papaverine induced full erection in the majority of patients (66%). In contrast to papaverine, the duration of erection induced by histamine was markedly shorter (mean 200 and 6.5 min, respectively). The penile erections induced by papaverine were associated with complications such as pain, haematoma and priapism. Histamine did not induce any complications. Treatment of eight male patients with psychogenic impotence with the histamine H1 receptor antagonist astemizol (10 mg orally once daily for 1 week) did not affect histamine-induced erectile responses. CONCLUSION: These results indicate that histamine may play a role in human penile erection. The erection-promoting action of histamine is probably due to H2 receptor activation, although another histamine receptor, possibly H3, also seems to be involved. This study suggests that histamine could be a valuable tool in the diagnosis of erectile dysfunction.