The thymus is thought to play a major role in the immunopathogenesis of human immunodeficiency virus (HIV) infection, particularly in maternal-to-fetal HIV transmission. Characteristic lesions of the HIV-infected thymus include a prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the region of the thymus where immune selection occurs. At least threefold excess early spontaneous abortions were noted in a cohort of 124 HIV-infected pregnant women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission was documented, with the thymus gland particularly affected. It is possible that the thymic insult in HIV-infected fetuses contributes to immune rejection of the fetus, possibly by an imbalance of maternal and fetal T1- and T2-type cytokines, known to be important in HIV disease progression. We propose, therefore, that the early spontaneous abortions occurring in HIV-infected pregnant women are due, at least in part, to abnormal immune forces created by HIV infection of the thymus.