On the buffalo ureter, histamine did not elicit any direct effect. However, it caused concentration-dependent relaxation of the tissues precontracted by carbachol, phenylephrine, norepinephrine, KCI or BaCl2 and also inhibited the contractile effect of carbachol. Metiamide selectively antagonised the relaxation and inhibition of contractile response but mepyramine did not show this effect. Isoprenaline, dobutamine, salbutamol, verapamil and papaverine neither produced any direct effect nor relaxed the carbachol-contracted tissues; norepinephrine and epinephrine had contractile effects. Hence, the histamine-induced relaxation was mediated through the activation of H2 receptors and not through adrenergic mechanisms or blockade of Ca(2+)-channels or inhibition of cyclic nucleotide phosphodiesterase.