Whether smoking habits influence ventilatory response to hypoxia and hypercapnia was examined in 23 pairs (8 concordant smoker pairs, 8 concordant nonsmoker pairs, and 7 discordant pairs) of monozygotic twins. Pulmonary function tests were also performed. Smokers (7 subjects) were significantly taller by 2 cm (mean value) than nonsmoker partners (7 subjects). Arterial pH of smokers was significantly lower, although it stayed within normal range. Closing volume to vital capacity ratio tended to be larger in smokers. Ventilatory response to hypoxia (slope factors for ventilation-alveolar Po2 curve and ventilation-arterial O2 saturation line) was significantly higher in smoking than in nonsmoking partners, whereas ventilatory response to hypercapnia (slope factor for ventilation-alveolar Pco2 line) was not different. Intrapair variances for height and ventilatory response to hypoxia were larger in discordant pairs with respect to smoking than in concordant pairs. These results indicate that smoking habits influence the slope, without the parallel shift, of the hypoxic ventilatory response curve.