BACKGROUND: Exclusive breast-feeding reduces the risk of respiratory illness in infants younger than 6 months of age in developing countries by approximately half. We evaluated the effect of exclusive breast-feeding on respiratory illness with fever (RIF) in Bangladeshi infants in the context of a randomized maternal influenza immunization trial. METHODS: Infants in a maternal vaccine trial in Dhaka, Bangladesh, were prospectively assessed at weekly intervals for 6 months after birth for breast-feeding practices and RIF. We estimated the risk of an RIF episode for infants who were exclusively breast-fed the prior week compared with infants not exclusively breast-fed the prior week using generalized estimating equations. RESULTS: We followed a total of 331 infants from birth to 24 weeks of age. The median weeks infants were exclusively breast-fed was 15 (interquartile range, 6-21). The adjusted independent odds of respiratory illness for exclusively breast-fed infants compared with nonexclusively breast-fed infants was 0.59 (95% confidence interval: 0.45-0.77) for an RIF episode. After adjusting for exclusive breast-feeding, we confirmed the previous report that maternal immunization with influenza vaccine had an independent protective effect against RIF (odds ratio, 0.72; 95% confidence interval: 0.55-0.93). No significant difference in the protective effect of exclusive breast-feeding was seen by maternal influenza immunization status. CONCLUSIONS: Exclusive breast-feeding during the first 6 months of life and maternal immunization with influenza vaccine independently and substantially reduced respiratory illness with fever in infants.