The role of histamine in acute hypoxic pulmonary hypertension was studied in dogs, and the correlation between the effect of histamine and the characteristics of hypoxic pulmonary response was examined. Acute hypoxic pulmonary vasoconstrictive response was not blocked by H1-receptor antagonist, but was potentiated by H2-receptor antagonist. Combined H1- and H2-receptor blockade failed to modify the hypoxic pulmonary vasoconstriction. It seems that H1-receptor antagonist could abolish the potentiating effect of H2-receptor antagonist. Exogenous histamine dilated lung vessels when pulmonary vascular tone was increased. This is in contrast to its vasoconstrictive effect when pulmonary vascular tone was normal. The vasodilating effect of histamine was blocked by H2-receptor antagonist. It is deduced that histamine probably plays the role of a modulator in hypoxic pulmonary vascular response. The dominant effect of H2-receptor caused by increasing pulmonary vascular tone might be implicated in the modulating effect. Infusion of histamine not only suppressed the pulmonary response to hypoxia, but also attenuated the progressive increase in pulmonary vascular resistance in repeated hypoxia. The reduction of the modulating effect of histamine probably contributes to the progressive increase in pulmonary vascular response to repeated hypoxia.