At rest and during exercise, noninvasive studies of cardiopulmonary physiology in patients with chronic obstructive pulmonary disease (COPD) were carried out to determine the objective benefits of commonly used oral bronchodilator drugs in 15 stable patients without cardiovascular disease or reversible obstruction of airflow. Theophylline, terbutaline, a combination of theophylline and terbutaline, and placebo were given for ten days each in a randomly sequenced double-blind protocol for outpatients. Spirometric values, the ratio of physiologic dead space to tidal volume (VDp/VT), and the alveolar-arterial oxygen pressure difference (P[A-a]O2) were studied at rest on each regimen. During steady-state exercise the changes in VDp/VT and P(A-a)O2, as well as the ventilatory equivalent for oxygen and oxygen pulse, were measured. When compared with placebo, no significant change was noted in the previously mentioned measurements with any regimen, with the exception of a small improvement in the forced expiratory volume in one second, which was significant for all regimens. These findings suggest that commonly used oral bronchodilator drugs in usual doses may have small effects on airflow even in "irreversible" COPD but that the objective effect of these agents on gas exchange during rest and exercise is not significant.