The effects of chronic exposure to moderate levels of carbon monoxide (CO) upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies. Cockerels were exposed to carefully regulated CO levels in dynamic exposure chambers. The plaque volume percentage in the aortic walls of experimental and control animals was determined by point-counting. Chronic CO inhalation, at levels up to 200 ppm, did not stimulate arteriosclerotic plaque development (at 200 ppm CO, carboxyhemoglobin (COHb) levels 10 min after exposures ended were 11-12%). When administered concomitantly with cholesterol feeding, CO did not augment plaque development. When administered after either carcinogen-associated or diet-promoted plaque size increases had occurred, CO elicited no further plaque size increases. Thus, in this animal model, daily exposures to moderately high CO levels were without discernable effect upon arteriosclerotic plaque development, although high COHb levels were attained.