A comparison of immune competence in 26 patients with Down syndrome in an institution and 26 matched healthy controls revealed an atypical pattern of T-cell immunodeficiency in the Down-syndrome patients. The patients with Down syndrome had a lymphocytosis in blood with high counts of T (and B) cells, but with impaired effector function of T cells as judged by anergy to dinitrochlorobenzene, low responsiveness to ubiquitous antigens which elicit delayed-type hypersensitivity reactions, and low mitogenic activity of non-stimulated and phytohaemagglutinin-stimulated lymphocytes in culture. Helper-T-cell function measured by the humoral immune response to flagellin was intact, and there were minor abnormalities of the B-cell system. Attempted restoration of T-cell function with levamisole was unsuccessful. This pattern of T-lymphocytosis with impaired effector function could be explained by "stress-deficiency" of the immune system consequent upon a heavy load of infection in early life.