Down syndrome (DS) thymocytes have a markedly diminished proportion of cells expressing high levels of the alpha, beta T cell receptor (TCR alpha, beta) and the associated CD3 molecule. Thus, we examined the surface expression of TCR alpha, beta and CD3 as well as TCR gamma, delta, CD4, CD8, CD16, and CD45RA on peripheral blood lymphocytes (PBL) from 13 noninstitutionalized subjects with DS and 13 closely age-matched sibling controls using immunofluorescence and flow cytometry. DS PBL expressed high surface levels of TCR alpha, beta and CD3, but, as compared to controls, they had a lower proportion of cells expressing TCR alpha, beta (61% vs. 68%, respectively; P less than or equal to 0.05). Moreover, the absolute number of TCR alpha, beta+ cells was considerably lower for DS subjects than for controls (1634 +/- 229 vs. 2763 +/- 530, respectively; P less than or equal to 0.05). DS subjects had a markedly higher proportion of cells expressing TCR gamma, delta than did the controls (12% vs. 7%, respectively; P less than or equal to 0.02). In addition, DS subjects had a lower proportion of CD4+CD45RA+ cells than controls (22% vs. 35%, respectively; P less than or equal to 0.02), representing naive T cells which have recently emigrated from the thymus. The imbalance in the proportions of T cell subpopulations we have observed in DS PBL may contribute to the increased susceptibility to infection associated with DS and may represent a diminished efficiency in the production of newly differentiated T cells by the DS thymus.