This prospective community-based study of infants born in inner London was undertaken to examine the association between premorbid airway function and subsequent wheezing in the first year of life and to explore the influence on this association of a family history of asthma and maternal smoking during pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and physician-diagnosed wheezing episodes were identified retrospectively from medical records. Specific airway conductance was determined from plethysmographic measurements of lung volume and airway resistance, before 13 wk and prior to any respiratory illness, in 101 infants, 28 of whom experienced at least one episode of wheezing during the first year. Mean (SD) specific airway conductance was significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s-1. kPa-1 and 2.60 (0.93) s-1. kPa-1, respectively (p < 0.05), and in those with a first-degree relative with asthma: 1.98 (0.83) s-1. kPa-1 and 2.60 (1.0) s-1. kPa-1, respectively (p < 0.05), but not in those whose mothers smoked during pregnancy, in whom airway resistance was, however, significantly elevated (p < 0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to 3.8) for every unit (s-1. kPa-1) decline in specific airway conductance (p = 0.02). After adjustment for premorbid airway function, the odds of wheezing were significantly increased in those with a family history of asthma (4. 3; 95% CI, 1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that impaired premorbid airway function precedes and predicts wheezing in the first year. Among those with a genetic predisposition to asthma, alterations in airway geometry or tone may increase susceptibility to wheezing. Maternal smoking has important and potentially preventable adverse effects on somatic growth and respiratory morbidity in early life.