SUMMARY. Since heart failure may occur in the setting of lung dysfunction and CO2 retention with only modest increases in cardiac work load, we questioned whether myocardial function is impaired by hypercapnic acidosis. To determine the influence of hypercapnic acidosis on right ventricular function, we measured the effects of acute (2 hours) and chronic (2 weeks) hypercapnic acidosis on right ventricular performance during normal and increased right ventricular afterload in five conscious dogs. Systemic hemodynamic and right ventricular functions were unaltered during normal right ventricular afterload by acute hypercapnic acidosis (Paco2 = 49 ± 3 mm Hg, pH = 7.27 ± 0.003). As right ventricular afterload was increased by progressive balloon occlusion of the right ventricular outflow tract during acute hypercapnic acidosis, the rise (slope) in right ventricular enddiastolic pressure was increased 4-fold (P < 0.01) over that observed in normocapnic control. Maximum isovolumic right ventricular dP/dt rose (P < 0.05) comparably with increasing right ventricular afterload during normocapnic control and acute hypercapnic acidosis. Chronic hypercapnic acidosis (Paco2 = 55 ± 2 mm Hg, pH = 7.28 ± 0.01) resulted in systemic vasodilation and increased (P < 0.05) heart rate and cardiac output during normal right ventricular afterload. As right ventricular afterload was increased during chronic hypercapnic acidosis, the rate of rise in right ventricular end-diastolic pressure was 2-fold (P < 0.01) above normocapnic control but maximum isovolumic right ventricular dP/dt was unchanged in contrast to normocapnic control and acute hypercapnic acidosis. Moreover, cardiac output fell and stroke work was unchanged with increasing afterload during chronic hypercapnic acidosis. /?-Adrenergic blockade resulted in an increased (P < 0.01) rate of rise in right ventricular end-diastolic pressure with afterload during normocapnic control and chronic hypercapnic acidosis. We conclude that hypercapnic acidosis results in diminished right ventricular performance during increased right ventricular afterload, evidenced by accentuated rise in right ventricular end-diastolic pressure, and may contribute to the congestive heart failure and edema observed in patients with pulmonary hypertension and CO2 retention.