Acute hypoxic pulmonary vasoconstriction can be inhibited by high doses of the carbonic anhydrase inhibitor, acetazolamide. This study aimed to determine if acetazolamide is effective at dosing relevant to human use at high altitude and to investigate whether its efficacy against hypoxic pulmonary vasoconstriction is dependent upon carbonic anhydrase inhibition by testing other potent heterocyclic sulfonamide carbonic anhydrase inhibitors. Six conscious dogs were studied in five protocols: 1. Controls, 2. Low dose intravenous acetazolamide (2mgxkg^-1xh^-1), 3. Oral acetazolamide (5mg/kg), 4. Benzolamide, a membrane-impermeant inhibitor and 5. Ethoxzolamide, a membrane-permeant inhibitor. In all protocols, unanesthetized dogs breathed spontaneously during the first hour (normoxia), and then breathed 9-10% O₂ for the next two hours. Arterial oxygen tension ranged between 35-39mmHg during hypoxia in all protocols. In controls, mean pulmonary artery pressure increased by 8mmHg, and pulmonary vascular resistance by 200dynxsxcm^-5 (p<0.05). With intravenous acetazolamide, mean pulmonary artery pressure and pulmonary vascular resistance remained unchanged during hypoxia. With oral acetazolamide, mean pulmonary artery pressure increased by 5mmHg (p<0.05), but pulmonary vascular resistance did not change during hypoxia. With benzolamide and ethoxzolamide, mean pulmonary artery pressure increased by 6-7mmHg, and pulmonary vascular resistance by 150-200dynxsxcm^-5 during hypoxia (p<0.05). Low dose acetazolamide is effective against acute hypoxic pulmonary vasoconstriction in vivo. The lack of effect with two other potent carbonic anhydrase inhibitors suggests that carbonic anhydrase is not involved in the mediation of hypoxic pulmonary vasoconstriction and that acetazolamide acts on a different receptor or channel.