Systemic and pulmonary vascular responses to infusions of histamine, 2-methylhistamine (2-MeH), and 4-methylhistamine (4-MeH) were determined. In dogs, H 1-receptor stimulation with 2-MeH induced pulmonary vasoconstriction, and a decrease in cardiac output. H 2-receptor stimulation with 4-MeH induced pulmonary and systemic vasodilation, tachycardia, and an increase in cardiac output. In cats, 2-MeH caused slight pulmonary vasoconstriction and 4-MeH caused vasodilation. Both H 1 - and H 2-receptors mediated the systematic vasodilation, tachycardia, and increase in cardiac output observed in cats.