This study was undertaken to evaluate the effect of in vivo cigarette smoke exposure on glutathione peroxidase--related enzyme systems of the rat lung. These enzymes, acting in concert, are thought to be responsible for disposing of toxic lipid peroxides in pulmonary tissue. Thirty-day-old rats were exposed to thirteen cigarettes per day for 21 days with a Walton reverse-smoking exposure apparatus. After 21 days of smoke exposure, the activities of glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase were increased 34%, 24%, and 38%, respectively, over control values. This level of cigarette smoke exposure did not cause detectable histological lesions. We present the hypothesis that short-term, low-level cigarette smoke exposure is capable of initiating metabolic alterations in lung cells at exposures at which histological changes are not detectable by light microscopy.