The effects of histamine were studied on the isolated circular muscle strip and longitudinal muscle strip of the dog portal vein. Histamine-induced contractions of the circular muscle were inhibited by H1-receptor antagonist pyrilamine but increased by H2-receptor antagonist ranitidine. When the tissues were contracted with PGF2 alpha in the presence of pyrilamine, histamine produced the relaxation of the circular muscle but not longitudinal muscle. The relaxation of the circular muscle was inhibited by ranitidine in a concentration dependent manner, the pA2 value for ranitidine being 6.97 (6.55-7.39). It is concluded that the response of the circular muscle to histamine is the sum of two components, H1-receptor mediated contraction and H2-receptor mediated relaxation.