Exercise tolerance in patients with COPD is difficult to predict from measurements of lung function. We examined multiple physiologic and psychosocial variables in an attempt to predict exercise performance in a group of patients with COPD enrolled in a clinical trial of pulmonary rehabilitation. A total of 119 patients (FEV1 = 1.41 +/- 0.64 L) were divided randomly into either a study group (group A, n = 58) or validation group (group B, n = 61). Stepwise multiple regression in group A revealed that peak oxygen uptake (peak VO2) was predicted best by the following equation: Peak VO2 (L/min) = (0.0327 x DCO) + (0.0040 x MVV)-(0.0156 x peak-exercise VD/VT) + (0.0259 x resting VE) + 0.848; r = 0.90; SE = 0.233 L/min. This equation was then cross-validated in group B. It demonstrated excellent validity: measured peak VO2 (L/min) = (1.13 x predicted peak VO2)-0.0891; r = 0.90; SE = 0.239 L/min. We conclude that exercise tolerance was predicted reasonably well from measurements of lung function and gas exchange in this group of patients with COPD. However, the variability of the prediction would limit its usefulness in individual patients.