We have investigated the relationship among the HIV-1 biologic phenotype, replicative capacity of virus isolates, HIV-RNA copy number in plasma, p24 antigenemia, CD4+ T lymphocyte counts in peripheral blood, and the clinical status in a cohort of 13 HIV-infected children younger than 12 mo of age, born of HIV-1 seropositive mothers. Six out of 13 HIV-1 isolates from these patients were classified as rapid/high and seven as slow/low. We have found a significantly positive correlation between the replication rate of HIV isolates and their capacity to induce syncytia in vitro. Most of the serial HIV-1 isolates obtained from infants with AIDS had the rapid/high phenotype and induced syncytia, whereas only two out of 23 HIV-1 isolates obtained from infants without AIDS showed these properties. In sequential analysis of HIV-1 isolates from infants with AIDS, the presence of viral isolates with rapid/high and SI phenotype was associated with higher levels of HIV-1 RNA in plasma, CD4+ T cell depletion, and clinical progression. By contrast, infants whose viruses exhibited nonsyncytium-inducing phenotype throughout the follow-up showed lower levels of HIV RNA, stable CD4+ T cell counts, and mild symptomatic HIV infection. Our findings indicate that infants who carried viruses with more cytopathic biologic phenotype and who had higher viral RNA coy numbers in blood were more likely to have lower CD4+ T cell counts and more likely to have AIDS.