Differences have been found in the cardiopulmonary responses to exercise between young male cigarette somkers and nonsmokers. The present study was undertaken in an attempt to determine the cause of such differences. Since smokers carry a chronically elevated carboxyhemoglobin level (>4%), carbon monoxide was inhaled by nonsmokers to raise their carboxyhemoglobin level to the range seen in a control group of smokers. This maneuver caused the development in nonsmokers of an increased oxygen debt with exercise and a reduced pulmonary diffusing capacity at rest. The changes after carbon monoxide inhalation were similar to those found when comparing smokers to nonsmokers. The pathogenesis of these changes are unknown, but support carbon monoxide as a possible etiologic factor accounting for the less efficient exercise and poorer pulmonary function performance of smokers compared to nonsmokers.