Term newborns can compensate fully for an imposed dead space (tube breathing) by increasing their minute ventilation. Objective: To test the hypothesis that infants of smoking mothers would have an impaired response to tube breathing. Design: Prospective study. Setting: Perinatal service. Patients: Fourteen infants of smoking and 24 infants of non-smoking mothers (median postnatal age 37 (11- 85) hours and 26 (10- 120) hours respectively) were studied. Interventions: Breath by breath minute volume was measured at baseline and when a dead space of 4.4 ml/kg was incorporated into the breathing circuit. Main outcome measures: The maximum minute ventilation during tube breathing was determined and the time constant of the response calculated. Results: The time constant of the infants of smoking mothers was longer than that of the infants of non-smoking mothers (median (range) 37.3 (22.2- 70.2) v 26.2 (13.8- 51.0) seconds, p = 0.016). Regression analysis showed that maternal smoking status was related to the time constant independently of birth weight, gestational or postnatal age, or sex (p = 0.018). Conclusions: Intrauterine exposure to smoking is associated with a dampened response to tube breathing. Objective: To test the hypothesis that infants of smoking mothers would have an impaired response to tube breathing. Design: Prospective study. Setting: Perinatal service. Patients: Fourteen infants of smoking and 24 infants of non-smoking mothers (median postnatal age 37 (11-85) hours and 26 (10-120) hours respectively) were studied. Interventions: Breath by breath minute volume was measured at baseline and When a dead space of 4.4 ml / kg was incorporated into the breathing circuit. Main outcome measures: The maximum minute ventilation during tube smoking was determined and the time constant of the response calculated. Results: The time constant of the infants of smoking mothers was longer than that of the infants of non-smoking mothers (median range 37.3 (22.2-70.2) v 26.2 (13.8- 51.0) seconds, p = 0.016). Regression analysis showed that maternal smoking status was related to the time constant independently of birth weight, gestational or postnatal age, or sex (p = 0.018). Conclusions: Intrauterine exposure to smoking is associated with a dampened response to tube breathing.