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As a model of breast milk transmission of HIV, we characterized humoral immune responses in the milk and plasma of 14 female rhesus macaques with suckling infants. Total immunoglobulin levels in plasma and milk were similar in all females and could not be correlated with transmission to the infant. These females, however, had elevated milk IgG levels and decreased milk IgA levels as compared with levels in seronegative controls. SIV envelope-specific antibody responses developed similarly in all females over the first 14-28 days after inoculation; however, 2 females had significantly lower titers by 98 days after inoculation. These females, characterized as rapid disease progressors, were the only animals to transmit SIV through breast-feeding during the period of acute viremia (14-21 days after inoculation). The remaining 12 females developed similar levels of high-avidity SIV envelope-specific IgG in plasma and low, but detectable, levels of IgA in milk. Despite similar quantities of antibody in milk, transmission of SIV through breast-feeding occurred in 8 of 12 mother-baby pairs during the chronic phase of disease. These observations are comparable with those for HIV-infected women and indicate that the SIV-macaque model provides a unique resource for deciphering the functional role of antibodies in breast milk transmission of HIV.