Histamine may play a role in many of the events occurring in the ovarian tissue and leading to ovulation. To elucidate the histaminergic influence on the ovarian vasculature, the mechanical response of the isolated rat ovarian artery to histamine and histamine agonists was investigated. Histamine relaxed the precontracted vessel segments in a concentration-dependent way, amounting to 82.7 +/- 4.3% of the papaverine-induced relaxation. This relaxant effect was counteracted by both the H1 antagonist, pyrilamine, and the H2 antagonist, cimetidine. That the effect of histamine was mediated by both histamine receptor subtypes was further confirmed by the relaxant effect produced in the presence of either of the H1-specific agonists, 2-pyridylethylamine and 2-methylhistamine on the one hand, and the H2-specific agonists, impromidine and 4-methylhistamine on the other. The H1 receptor-induced relaxation was mediated via an effect on the endothelium, whereas the H2 receptor-mediated relaxation was mostly a direct effect on the smooth musculature in the vessel wall. No major differences in the mechanical response of the rat ovarian artery were seen during the different stages of the estrous cycle, although at late proestrus, just before ovulation, the maximum relaxation induced by histamine was particularly high, in spite of a low sensitivity of the receptors for the amine.