Patients after pneumonectomy are severely limited upon exercise, but impairments in gas exchange are generally mild. One potential explanation of this observation is the existence of functional reserves of diffusing capacity (DLCO), which may be recruited during exercise, predominantly by increasing pulmonary blood flow (Qc). After pneumonectomy, DLCO reserves are recruited even at rest. To investigate if the pattern of recruitment of DLCO is altered and if reserves of DLCO are exhausted during exercise after pneumonectomy, DLCO, lung volume, and cardiac output were measured by the rebreathing method at rest and at multiple levels of steady-state exercise in eight subjects after pneumonectomy and in eight age- and sex-matched nonsmoking normal subjects. In patients after pneumonectomy, the slopes of increase in DLCO [ml.(min.mm Hg)-1.m-2] with respect to QC [ml.min-1.m-2] were normal (0.91 +/- 0.09 x 10(-3) in the pneumonectomy group, 1.16 +/- 0.12 x 10(-3) in the control group, mean +/- SE, p less than 0.05). Thus, the pattern of DLCO recruitment was not significantly affected by pneumonectomy. The ratio of DLCO/Qc fell more rapidly during exercise in patients after pneumonectomy, but the lowest value of the ratio achieved was relatively normal in all except one patient. Declines in arterial O2 saturation at exercise were mild and insufficient to explain the exercise limitation except in the patient whose DLCO/Qc fell below normal. There was no evidence that an upper limit of recruitment was approached. We conclude that the normal ability to recruit DLCO during exercise after pneumonectomy constitutes an important compensatory feature that prevents significant arterial O2 desaturation. In most patients, exercise is limited by a reduced maximal stroke index before reserves of diffusing capacity are exhausted.