To ascertain whether thymic lymphocytes represent suitable targets for HIV-1 infection, we infected thymic cell suspensions from normal donors with HIV-1 (HTLV-IIIB strain). We found that, in vitro, thymic lymphocytes are readily infected and highly permissive for HIV-1 replication. In addition, immature cells with the CD4+/CD8+ phenotype, most likely the precursors of mature circulating CD4+ and CD8+ lymphocytes, showed a marked susceptibility to viral infection and replication. These findings suggest that thymus infection may play a triggering role in the pathogenesis of AIDS, particularly in pediatric cases, and may partially explain the lack of restoration of peripheral CD4+ lymphocytes killed by HIV-1.