Veins were isolated from 16 sites of the rabbit venous tree and responses to histamine and histamine receptor agonists were studied to characterize the histamine receptors. Isometric contraction and relaxation of ring segment preparations were recorded. Histamine produced concentration-dependent contractions in all veins in the resting state. Both the maximum response and pD2 value varied remarkably from vein to vein and regional differences in sensitivities to histamine varied considerably from previous findings in dog veins. Also in the precontracted state with a vasoconstricting agent, histamine predominantly contracted the veins. The contractile responses to histamine, in both resting and precontracted states, were antagonized competitively by the histamine H1-receptor antagonist, mepyramine. On the other hand, histamine relaxed the precontracted veins, in the presence of mepyramine. Selective H2-receptor agonists, dimaprit and impromidine, relaxed the precontracted veins even in the absence of mepyramine. These responses to histamine were antagonized competitively by the H2-receptor antagonist, cimetidine or ranitidine. The present study provides quantitative and systematic data regarding histamine receptors in rabbit veins. We propose that: 1) there are both vasoconstrictor H1-receptors and vasodilator H2-receptors, 2) histamine generally contracts rabbit veins through predominant H1-receptors and that 3) the H2-receptor-mediated relaxation does not depend on the presence of the endothelium.