The presence of Ia-like antigens was demonstrated on a small population (2-6%) of highly purified human circulating T lymphocytes by immunofluorescence with a rabbit anti-Ia serum raised against the isolated bimolecular Ia structure. The Ia+ T lymphocytes have no surface or intracellular immunoglobulins. The expansion of this Ia+ T-cell population was encountered in certain patients. Ia antigens were also found on T blasts grown in long-term cultures with conditioned medium generated by phytohemagglutinin-stimulated lymphocytes. In addition, leukemia blasts which stained for Ia antigens and formed E rosettes were identified in the peripheral blood of two leukemic patients. This evidence further supports the existence of Ia-bearing T cells in man. The Ia+ T-lymphocyte population was shown to contain cells responsible for the generation of allogeneic helper activity. Elimination of Ia+ lymphocytes from a purified T-cell population by the anti-Ia antiserum and complement abolished its ability to help an allogeneic B-cell preparation to generate plaque-forming cells against sheep erythrocytes in vitro in the presence of the antigen.