Possible interactions of ozone and cigarette smoke exposure have been tested in 2-hr chamber exposures of 26 male and 6 female subjects, all of whom were habitual smokers. Treatment conditions were air alone, air + cigarette smoking, ozone alone, and ozone + cigarette smoking. Ozone levels were increased progressively over four trials (0.37 ppm, 0.75 ppm, 0.50 ppm + intermittent exercise, and 0.75 ppm + intermittent exercise); exercise (50 W for 15 min alternating with 15-min rest) was intended to increase ventilation by a factor of 2.5. Ozone exposure reduced the carbon monoxide intake normally seen with smoking, as judged from smaller increments of blood carboxyhemoglobin readings. Ozone exposure alone gave rise to a decrease of lung function (forced vital capacity (VC), 1-sec forced expiratory volume, and maximum flow rates at 25 and 50% of VC), but the onset was slower and the response less dramatic than previously seen in nonsmokers, suggesting that the chronic effect of smoking may be to delay bronchial irritation by ozone. Smoking increased heart rate both at rest and during exercise, but this response was not materially influenced by simultaneous ozone exposure. It is concluded that over an acute 2-hr exposure, there is no appreciable interaction between cigarette smoking and responses to ozone.