Exclusive breast feeding has been associated with a lower rate of mother-to-child HIV transmission than breast feeding plus other foods. To obtain further information on biologic outcomes of different feeding modes, we examined 272 infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test. In a subset of infants, urinary neopterin excretion was measured as an indicator of immune system activation. Infants who had themselves become HIV-infected by 14 weeks had higher ( p <.01) intestinal permeability at 6 and 14 weeks and slightly (.05 < p <.1) higher neopterin excretion at all times than uninfected infants. At 1 week infants given no breast milk had higher ( p <.05) intestinal permeability than infants given breast milk exclusively or with other foods. Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants. Feeding mode had no effect on neopterin excretion. Thus, infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent. The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother-to-child transmission of HIV.