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Sixteen children over the age of 5 years (Group 1) have been identified out of 537 children infected by human immunodeficiency virus and born to HIV-infected mothers, in Kigali, Rwanda. They were followed up for 2 years and compared with 16 younger AIDS patients (Group 2) and with 16 age- and gender-matched HIV-1 seronegative children (Group 3). Fourteen Group 1 subjects had anti-HIV-1 IgM which persisted during the entire study period, in 11 cases directed to HIV-1 envelope proteins. In vitro, immortalization of B lymphocytes by the Epstein-Barr virus confirmed a high production of IgM to envelope proteins. All these patients had anti-p 17 IgG which was not observed in 7 patients from Group 2. All 16 children mounted significant titers of neutralizing antibodies to HTLV-IIIB, and, in 8 patients tested, against two other HIV-1 strains, RII and MN. HIV-1-specific major histocompatibility complex (MHC)-restricted cytotoxic T cells were demonstrated in 3 of 5 of the subgroup who were tested. Prolonged survival over 5 years in children with maternally acquired HIV-1 infection is associated with a high titer of neutralizing antibodies, a persistent production of IGM to HIV-1 envelope proteins and of IgG to p 17.