BACKGROUND: Transmission of HIV-1 through breastfeeding is a major problem, although its timing is not well characterized. METHODS: The authors examined the timing and correlates of HIV-1 transmission through breastfeeding among 1078 HIV-infected pregnant women from Dar es Salaam, Tanzania enrolled in a trial to examine the effect of vitamin A and other vitamin supplements on mother-to-child transmission of HIV-1 and other health outcomes. Cumulative incidence was measured among children of women not randomized to vitamin A (n = 312), given the higher risk of infection observed among those in the vitamin A arm. For analyses of correlates, data from all children not infected by age 6 weeks were used (p = 659). RESULTS: Mean duration of breastfeeding was 20.3 months (SD = 4.4 months; median = 20.5 months). Thirty-seven infections were observed during 4372 child-months of follow-up evaluation, or 10.2 cases per 100 child-years. Infection risk by age 4 months was 3.8% (95% confidence interval [CI], 1.6%-6.1%) and increased to 17.9% (95% CI, 11.2%-24.5%) by age 24 months. In a multivariate proportional hazards model, high maternal viral load (p =.0001), low CD4 cell count (p =.004), and high maternal erythrocyte sedimentation rate (ESR; p=.004) were significant predictors of transmission of HIV-1 through breastfeeding. Mothers who had breast lesions during pregnancy were 2.00 times more likely to transmit the virus during breastfeeding than mothers without these lesions (95% CI, 1.29-3.08; p=.002). CONCLUSIONS: The rate of breastfeeding transmission of HIV-1 is high, and early weaning is likely to be associated with reduced transmission. Antiretroviral drugs given to HIV-infected mothers are likely to reduce the risk of breastfeeding transmission. In their absence, interventions that enhance immune reconstitution, such as micronutrient supplements, may be beneficial against transmission. Methods to prevent and treat nipple cracks and mastitis may also be important.