The right ventricular (RV) response to upright bicycle exercise was assessed in 16 patients with chronic obstructive pulmonary disease (COPD), in 23 patients with coronary artery disease (CAD), and in 19 normal control subjects. Right ventricular (RV) and left ventricular (LV) ejection fractions were determined noninvasively using first-pass quantitative radionuclide angiocardiography, a technique well suited for simultaneous assessment of RV and LV systolic performance. The factors limiting exercise in COPD and CAD are distinctly different, and therefore patients with COPD were studied by means of a single-stage submaximal exercise test, while patients with CAD were studied by means of a graded maximal test. The normal response to exercise, irrespective of exercise protocol, was at least a 5% increase in RV and LV ejection fractions. In 12 of 16 patients with COPD, RV ejection fraction either decreased or remained the same with exercise (abnormal exercise RV reserve). Left ventricular exercise reserve was abnormal only in five patients, probably due to occult CAD. Isolated abnormal exercise RV reserve was present in nine patients. The severity of ventilatory impairment and resting arterial hypoxemia were major determinants of abnormal exercise RV reserve in patients with COPD. In 12 of 23 patients with CAD, RV ejection fraction either decreased or remained the same with exercise (abnormal exercise RV reserve). Left ventricular reserve was abnormal in 18 of 23 patients; RV exercise reserve was abnormal only in CAD patients with concomitant abnormal LV reserve. The presence of proximal right coronary artery stenosis (the major blood supply to the RV) was not a significant determinant of the RV response to exercise in patients with CAD. These data suggest that abnormal exercise RV reserve occurs frequently both in COPD and CAD patients. In COPD the predominant hemodynamic abnormality involves performance of the RV, while in CAD the predominant abnormality involves the LV. The common factor modulating RV exercise performance in both diseases appears to be altered RV afterload.