Although chronic exposure to carbon monoxide (CO) or high altitude produces pronounced cardiovascular changes in humans as well as animals, there is little information on the effects elicited by these stressors combined. Theoretical considerations, as well as data from acute studies, suggest that CO inhaled at high altitude may be more detrimental than CO inhaled at low altitude. The purpose of these studies was to construct a system in which CO and altitude could be controlled precisely, and to investigate the effects of continuous exposure to CO and high altitude on body weights and hematocrit ratios, as well as heart, spleen, adrenals, kidneys, and pituitary weights. Male, laboratory rats were exposed for 6 wk in steel barometric chambers to (1) 100 ppm CO, (2) 15,000 ft simulated high altitude (SHA), and (3) CO at SHA. Altitude was simulated by a system of gate valves and a vacuum pump, and measured by an altimeter. CO, from high-pressure cylinders, was introduced into the air supplying each chamber through a mass flow controller and measured by a nondispersive infrared (NDIR) analyzer. Although SHA had no affect on left ventricle plus septum (LV + S), adrenal, spleen, or kidney weights, SHA decreased body weights, and increased hematocrit ratios, as well as right ventricle (RV), total heart (HT), and pituitary weights. CO had no affect on body weights, RV, HT, adrenal, spleen, or kidney weights, but CO increased hematocrit ratios and LV + S weights. There was no significant interaction between SHA and CO on any parameter except kidney weight. These results indicate that, in general, the effects produced by 15,000 ft SHA are not intensified by exposure to 100 ppm CO.