Thirty patients 38-75 years of age who had ischemic heart disease were studied to assess the effect of acute elevation of carboxyhemoglobin (COHb) concentration. After an initial familiarization and exercise session patients were exposed to air (carboxyhemoglobin (COHb) = 1.5 + 0.05%) and to carbon monoxide (CO) (100 ppm-CIHb-average = 3.8 + 0.1%) on successive days in a double blind, randomized fashion. There was no significant difference in time to onset of angina (air = 312, CO = 306 sec), maximal exercise time (air = 711 sec, CO = 702 sec) maximal ST depression (1.5 min for both), or time to significant ST depression (air = 474 sec, CO = 475 sec). Double product at ST depression and maximal double products were similar for both conditions. Resting ejection fraction was slightly but nonsignificantly higher after CO exposure (air = 53.9%, CO = 55.2%) Maximal ejection fraction was similar for both conditions (air = 57.4%, CO = 57.1%). Change in ejection fraction was slightly lower for CO exposure (air = 3.5%, CO = 2%), p = .049. In conclusion, there is no clinically significant effect of 3.8% COHb (representing a 2.2% increase from resting values) on the cardiovascular system in the study.