The response of the longitudinal and circular myometrial strips to histamine was studied in oestrogentreated rats. Histamine produced a dose-related inhibitory response in KCl-contracted longitudinal and circular uterine strips. Histamine was equipotent in producing the relaxant response but the maximal effect achieved in the longitudinal muscle was higher than the circular one. Ranitidine antagonized the histamine-induced relaxation with a similar dose ratio in both longitudinal and circular strips. Clemizole and reserpine treatment did not produce any modification of the dose-response curve to histamine. In the longitudinal and circular strips which were not preconstricted by KCl, neither histamine nor 2-pyridylethylamine, even in strips pretreated with ranitidine, produced any effect when added to the organ bath. Our results show that the response of histamine in both longitudinal and circular uterine layers of the oestrogen-treated rats are mediated exclusively by histamine H₂-receptors.