Calves aged 2-4 mo. living at high (11,000 ft.) altitude showed a large pulmonary pressor response to intravenous doses (100 [mu]) of adeno-sine triphosphate (ATP). This led us to study the pressor response in normal valves to mono-, di-, and triphosphate nucleotides derived from purines (adenine, guanine, inosine) and pyrimidines (uridine, cytosine). Greater pulmonary pressor responses occurred with di-, than triphosphates and with purine than pyrimidine compounds. As little as 5 [mu] of ADP, the most potent compound tested, caused detectable rises in pulmonary arterial pressure. A concomitant decrease in arterial platelets suggested these were trapped in the lung vessels obstructing pulmonary blood flow. Daily administration for 1-4 wk. of 100 [mu] ADP caused intimal swelling and proliferation and medial hypertrophy. Acute and chronic administration of small doses of certain high-energy nucleotides causes profound alteration in structure and function of pulmonary arteries.