T cell differentiation antigen expression by thymocytes from nine individuals with Down syndrome (DS) and 27 controls was examined using immunofluorescence and flow cytometry. We found no significant differences between DS and controls in the proportion of CD1+ or CD2+ cells or in the percentages of CD4-8-, CD4+8+, CD4-8+, or CD4+8- cells. However, a significantly smaller proportion of cells expressing high levels of T cell receptor alpha, beta (TCR alpha, beta) was observed in DS thymuses compared to controls (28.0% vs 47.5%, respectively; P less than or equal to 0.01). A similar observation was made for CD3, a signal-transducing complex for the TCR, where the proportion of cells expressing high levels of CD3 in DS was 24.3% compared to 53.3% for controls (P less than or equal to 0.001). These data demonstrate aberrant T cell maturation in DS. Furthermore, our observation of diminished expression of critical molecules for antigen-specific recognition by T cells suggests a possible mechanism for decreased T cell function in DS.