The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.