The present investigation studied the effects of hydrogen ion concentration on pulmonary vascular reactivity to the biogenic amines in vitro. Pulmonary arterial segments from cats were dissected free of surrounding tissue and endothelium and isometrically suspended in tissue baths. Cumulative dose-response curves were constructed to norepinephrine, histamine, serotonin, and potassium chloride, and the protocol was designed such that only one agent and hydrogen ion concentration was studied in each vessel segment. Alkalosis ([H+] less than or equal to 28 nmol/l) produced enhanced maximum responses to all of the agents used in this study. Acidosis [( H+] greater than or equal to 52 nmol/l), in contrast, was without effect on the maximum responses to histamine, serotonin, and potassium chloride, but did produce increased maximum responses to norepinephrine. No alterations in the ED50 of the dose-response curves were observed for any of the agents tested. In general, increases in sloped of the dose response curves were correlated with hydrogen ion concentrations that demonstrated increased maximum responses, suggesting that the present observations may have resulted from hydrogen ion-induced changes in amine receptor efficacy. The present data demonstrate that (1) as in the in vivo model, pulmonary vascular amine receptor activity is related to the hydrogen ion concentration; (2) there are two hydrogen ion concentration ranges where adrenergic receptor activity was observed to be enhanced; (3) the effects of acidosis where specific for the adrenergic receptor system, since the reactivity to only norepinephrine was significantly altered by acidosis; and (4) the effects of alkalosis may have resulted from increased overall contractility of the pulmonary vascular smooth muscle cells, since the force developed to all the agents tested was enhanced by alkalosis.