The CO2 rebreathing method, a noninvasive indirect Fick procedure, was previously validated in normal subjects at supine rest and during exercise. Nearly simultaneous measurements (29) of cardiac output were made by CO2 rebreathing and dye dilution in 17 patients with cardiovascular disease, 11 with hypertension and 6 with congestive heart failure. Cardiac output at supine rest averaged 5.52 .+-. 0.31 l/min by CO2 and 5.62 .+-. 0.32 l/min by dye dilution (r = 0.93). Successive cardiac output measurements by rebreathing varied 6.0 .+-. 1.1% (r = 0.96) and by dye dilution, 6.5 .+-. 0.9%. Changes in cardiac output during exercise or after .beta.-adrenergic blockade were reflected by the CO2 method. The CO2 method provides reliable measurements of cardiac output both at rest and during exercise in patients with hypertension or congestive heart failure. Further validation of the method is needed in various disease states before it can be widely applied.