Right ventricular ischemia occurs in experimental models of pulmonary hypertension. We analyzed right ventricular size and function and Tl-201 uptake to determine if there was a relationship between Tl-201 uptake and systolic function in 19 patients with pulmonary artery hypertension who were being evaluated for heart-lung transplantation. All patients had dipyridamole stress Tl-201 scintigraphy, radionuclide angiography and echocardiography. In nine patients (Group 1), right ventricular ejection fraction was <30% (mean 22% +/- 8%). In 1 0 patients (Group 2) it was > 30% (mean 45% +/- 11%). In Group 1, right ventricular Tl-201 uptake in the lateral wall after dipyridamole was increased compared to Group 2 (40% +/- 7% versus 28% +/- 15% counts/pixel, p < 0.05) while left ventricular free wall uptake was similar. The ratio of right to left ventricular Tl-201 uptake was increased in Group 1 versus Group 2 (0.81% +/- 0.30% versus 0.49% +/0. 18%, p < 0.05). At 4 hr, right ventricular free wall Tl-201 clearance was comparable, 51% +/- 13% versus 51% +/- 18% in Groups 1 and 2, respectively. No patient had perfusion abnormalities. Right ventricular ejection fraction was inversely related to dipyridamole stress right ventricular Tl-201 uptake, r = -0.49, p < 0.03, s.e.e. = 13.6. Right ventricular Tl-201 uptake was directly related to right ventricular wall thickness (r = 0.56, p = 0.18, s.e.e. = 10.4). Therefore, patients with more severe right ventricular systolic dysfunction have greater Tl-201 uptake after dipyridamole stress, suggesting increased myocardial mass and possibly blood flow in response to hypertrophy. Patients with the most marked hypertrophy have impairment of right ventricular systolic function, independent of ischemia.