During a longitudinal study of lung function and airway responsiveness in a cohort of healthy infants, we identified a subgroup of symptom-free infants at the age of 1 month with flow limitation during tidal expiration. We report a 2-year follow-up of 252 infants who were first studied at 1 month of age. Maximal flow at functional residual capacity (VmaxFRC) was measured from a forced expiratory flow-volume curve by the rapid thoracic compression technique. The pattern of tidal breathing was assessed with the ratio of the time to reach maximal expiratory flow during expiration to the total expiratory time (Tme/Te ratio). Histamine inhalation challenge was used to determine the level of airway responsiveness. Compliance and resistance of the total respiratory system were measured from a passive expiration after occlusion at end inspiration. Data regarding the family history of asthma, atopy, and parental smoking were obtained by questionnaire. Flow limitation was considered present when the forced expiratory flow did not exceed tidal flow at functional residual capacity. Nineteen infants were identified with flow limitation at 5 weeks of age; all had a family history of asthma, atopy, and/or parental smoking. These 19 infants were compared with 35 infants with no family history of asthma or parental smoking and 38 gender-, history-, and age-matched control infants without flow limitation during tidal expiration. At the age of 1 month, the flow-limited group had reduced VmaxFRC, Tme/Te, and respiratory compliance and increased respiratory resistance. At 6 and 12 months of age, although no longer flow limited, these infants still had significantly reduced lung function and increased airway responsiveness. Flow limitation in early life was also significantly associated with the development of physician-diagnosed asthma by the age of 2 years (odds ratio, 7.4; 95% confidence interval, 1.4 to 35.2). Infants with abnormal lung function soon after birth may have a genetic predisposition to asthma or other airway abnormalities that predict the risk of subsequent lower respiratory tract illness.