Acute exposure to carbon monoxide has the potential to impair exercise capacity in patients with ischemic heart disease. The effect of sufficient inhalation of this compound to gradually produce a level of 6% carboxyhemoglobin was studied in 30 nonsmoking patients with obstructive coronary artery disease and evidence of exercise-induced ischemia. After an initial training session, subjects were exposed to air or carbon monoxide on successive days in a randomized double-blind crossover fashion. Cardiac function and exercise capacity were assessed during symptom-limited supine radionuclide ventriculography. On the carbon monoxide day, mean postexposure carboxyhemoglobin was 5.9 +/- 0.1% compared with 1.6 +/- 0.1% (p less than 0.01) after air exposure. The mean duration of exercise was significantly longer after air compared with carbon monoxide exposure (626 +/- 50 s for air versus 585 +/- 49 s for carbon monoxide, p less than 0.05). Actuarial methods suggested that subjects were likely to experience angina earlier during exercise on the day of carbon monoxide exposure (p less than 0.05). Both the level (62 +/- 2.4 versus 60 +/- 2.4%, p = 0.05) and change in left ventricular ejection fraction at submaximal exercise (1.6 +/- 1.6 versus -1.2 +/- 1.6%, p = 0.05) were greater on the air exposure day compared with the carbon monoxide day. The peak exercise left ventricular ejection fraction was not different for the two exposures (57 +/- 2.5% for both). These results demonstrate earlier onset of ventricular dysfunction, angina and poorer exercise performance in patients with ischemic heart disease after acute carbon monoxide exposure sufficient to increase blood carboxyhemoglobin to 6%.