Abnormal proportions of the distinct T cell subpopulations binding the Fc portion of IgM (T-M) cells and those bearing receptors for the Fc portion of IgG (T-G) cells, were observed in blood samples from patients who had congenital or acquired abnormalities of the thymus, severe combined immunodeficiency, or an unexplained primary deficiency in cell-mediated immunity; most had too few circulating T-M cells and often an overabundance of T-G cells. In an in vitro evaluation of lymphocyte from one of three thymoma patients with an elevated T-G subpopulation, removal of T-G cells abrogated the suppression of T-M cell help of B cell differentiation induced by pokeweed mitogen. A spectrum of patients with sex-linked infantile agammaglobulinemia, variable hypogammaglobulinemia, and selective IgA deficiency, and a few patients with autoimmune syndromes infrequently had distorted representation of these T cell subpopulations in the circulation. This suggests that B cell dysfunction in many of these patients is not merely due to numerical excesses or insufficiencies of helper or suppressor T cells.