The relationship between initial level of lung function and subsequent wheezing, lower respiratory illness (LRI) was studied in 97 infants in whom the first measurement of pulmonary function (PFT) was made before 6 months of age. Occurrence of LRI was evaluated by standardized questionnaires at each well-baby visit, biweekly telephone calls to mothers, and review of all visits to physicians. Infant PFT was assessed by partial expiratory flow-volume curves and helium-dilution measurement of functional residual capacity (FRC). Maternal, prenatal smoking was assessed by urine cotinine and standard questionnaires. Infants who developed an LRI during the first year of life had lower preillness length-corrected forced expiratory flow at FRC (VFRC) than those who did not experience an LRI (males, 2.06 +/- 0.20 versus 2.32 +/- 0.29 ml/s/cm; females, 2.38 +/- 0.20 versus 2.91 +/- 0.26 ml/s/cm). Similar results were observed with FRC-corrected VFRC. No differences were observed for FRC. Differences in lung function were greatest in female infants whose mothers did not smoke during pregnancy (VFRC 2.67 +/- 0.25 versus 3.49 +/- 0.26 ml/s/cm for those with and without LRI, respectively; p = 0.03). History of maternal wheezing was more common in infants who experience an LRI, independent of maternal smoking. The results were not influenced by exposure to nonmaternal sources of environmental tobacco smoke in the postnatal period. Regression analyses that included data for multiple measurements of VFRC over the first year and took account of duration of follow-up demonstrated that lower levels of VFRC were associated with an increased frequency of LRI, especially in female infants.(ABSTRACT TRUNCATED AT 250 WORDS)