Carboxyhemoglobin (COHb) values were determined in mice exposed to varying amounts of marijuana and tobacco cigarette smoke utilizing a spectrophotometric technique. Mice were exposed to smoke inhalation in a modified Walton horizontal smoke exposure machine, whereby rodents can be exposed to multiples of 1-min smoke exposure cycles. Smoke exposure was intermittent; during the first 30 sec of each 1-min cycle, the subjects were exposed to smoke diluted either 1:10 or 1:5 with air. During the second half of the cycle the animals were given fresh air. There was a positive linear relationship between COHb values obtained and the number of puffs of marijuana smoke administered via either 2, 4, 6, or 8 "puffs" of marijuana smoke. COHb levels in plasma did not increase in animals given multiple 8-puff episodes of smoke daily as long as a 60-min period was interposed between smoking episodes. COHb values in mice exposed to tobacco smoke were significantly higher than those in mice receiving equal numbers of exposures to marijuana smoke. Mean COHb values of mice receiving 8 consecutive puffs of marijuana smoke were 18.6 and 22.0% saturation, but CO was rapidly cleared from the blood. This rapid clearance suggests that the binding affinity of CO for mouse hemoglobin may be be weaker than that of human hemoglobin. Mice similarly exposed to 6 or 8 puffs of tobacco smoke had mean COHb values of 24.6 and 28.5% saturation, respectively. No acute lethal effects were observed in mice receiving multiple daily episodes of 8 puffs per episode of marijuana smoke, whereas mice exposed to a single 8-puff episode of tobacco smoke suffered about 50% acute lethal effects.