The present work investigates in vitro the inhibitory dose-response curves to histamine, 4-methyl-histamine and 2-pyridylethylamine in depolarized (KCl 37 mM) uterus from estrogenous sensitized rats. 2. Dose-response curves for the various agonists were obtained in the absence and presence of selective histaminergic (clemizole and cimetidine) and adrenergic (propranolol and reserpine) blocking drugs. 3. Histamine and 4-methyl-histamine, but not 2-pyridylethylamine, produced dose-dependent relaxations of the uterus. 4. Neither clemizole nor propranolol displaced the inhibitory dose-response curves for histamine. 5. After adrenergic blockade with either propranolol or reserpine, cimetidine produced a rightward displacement of the dose-response curves to histamine. 6. Theses results suggest that the inhibitory effect of histamine is mediated through activation of H2 histamine uterine receptors.