Breast-feeding as a route of HIV-1 transmission during infancy but also as a protective measure against early childhood morbidity has been investigated prospectively in children born to HIV-1-seropositive mothers and control children born to age- and parity-matched HIV-1-seronegative women. The mothers of all study children had been enrolled antenatally at a maternity hospital in Kinshasa, Zaire, which served a relatively affluent group of women who sometimes chose not to breast-feed their infants. In 106 children born to HIV-1-seropositive women, the rate of HIV-1 transmission was 21% in 28 infants exclusively breast-fed, 19% in 68 infants both breast- and bottle-fed and 0% in 10 infants who were bottle-fed only (P = 0.35). In contrast, non-HIV-1-infected children of both HIV-1-seropositive and HIV-1-seronegative mothers who were exclusively breast-fed compared with uninfected children who were not exclusively breast-fed had significantly lower incidence rates of acute diarrhea, fever and lower respiratory tract infection. The lack of a dose-response effect between breast-feeding and perinatal HIV-1 transmission and the presence of a protective effect of breast-feeding against common causes of early childhood morbidity and mortality support the current World Health Organization recommendation that breast-feeding should continue to be promoted in all developing countries, including those with high HIV-1 prevalence rates in women of childbearing age.