The harmful effects of passive cigarette smoke exposure to infants include an increased frequency of asthma exacerbations, lower respiratory viral infections, and the sudden infant death syndrome (SIDS). Because of a difficulty in obtaining airway tissue from infants, little information is available on the effects of passive cigarette smoke exposure on the structure of the infant airway wall. We examined airway dimensions in 19 children who died from SIDS whose mothers smoked more than 20 cigarettes a day prenatally and postnatally, and compared these data with those from 19 infants who died from SIDS and had nonsmoking mothers. Total inner and outer wall areas were calculated for each airway and expressed in terms of the basement membrane perimeter (Pbm). Inner airway wall thickness was greater in the larger airways of those infants whose mothers had smoked more than 20 cigarettes a day. These findings suggest that infants exposed to a high level of passive cigarette smoke develop significant structural changes in their airways. Increased airway wall thickness may contribute to exaggerated airway narrowing and may help explain the previously observed abnormalities in neonatal lung function that have been described in infants of smoking mothers.