Background: Asthma prevalence has increased dramatically in recent years, especially among children. Breast-feeding might protect children against asthma and related conditions (recurrent wheeze), and this protective effect might depend on the duration and exclusivity of the breast-feeding regimen. Objective: We sought to determine whether there is an association between breast-feeding and asthma, recurrent wheeze, or both in children up to 72 months of age and whether the duration and exclusivity of breast-feeding affect this association. Methods: Data were from the third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey conducted from 1988 to 1994. We tested for significant associations between breast-feeding and physician-diagnosed asthma and recurrent wheeze (≥3 episodes in the past 12 months) before and after adjusting for potential confounders. Results: Crude analyses showed that breast-feeding was associated with significantly reduced risks for asthma and recurrent wheeze in children 2 to 71 months of age, but after adjusting for potential confounders, these overall protective associations attenuated and were no longer statistically significant. However, 2 new and important associations were revealed after adjusting for confounders: (1) compared with never breast-fed children, ever breast-fed children had significantly reduced odds of being diagnosed with asthma and of having recurrent wheeze before 24 months of age, and (2) among children 2 to 71 months of age who had been exposed to environmental tobacco smoke, those who had ever been breast-fed had significantly reduced risks of asthma and wheeze compared with those who had never been breast-fed. Conclusions: Breast-feeding might delay the onset of or actively protect children less than 24 months of age against asthma and recurrent wheeze. Breast-feeding might reduce the prevalence of asthma and recurrent wheeze in children exposed to environmental tobacco smoke. (J Allergy Clin Immunol 2003;111:328-36.)