To evaluate the possible effect of zinc treatment on immune disorders in children with Down's syndrome (DS), 38 noninstitutionalized DS children were investigated. Twenty-four patients (63.2%) had plasmatic zinc levels lower than 0.70 microgram/dl ("hypozinkemic," LZn) and 14 patients (36.8%) had levels higher than 0.75 microgram/dl ("normozinkemic," NZn). No correlation was found between the zinc deficiency and recurrence and/or intensity of infections. The absolute numbers of peripheral lymphocytes, the percentages of B lymphocytes, total T cells, and serum IgG, IgA, and IgM levels did not differ between the DS children and the controls. Eight (21%) patients had CD4+ T cell counts below the lowest value for the controls. Seventeen (44%) DS patients had increased levels of CD8+ T cells. The mean percentage of Leu 7+ cells in DS subjects (22.8 +/- 12.9%) was significantly higher than that in controls (15.8 +/- 4.8%) (P less than 0.01). Notably, Ig levels and numbers of lymphocytes in each subset did not show any significant difference in NZn and LZn trisomic subjects. On the contrary the peripheral blood mononuclear cells (PBMCs) from LZn DS children showed a significantly lower proliferative response to phytohemagglutinin (PHA) (S.I. = 23.4 +/- 22.4) than that of PBMCs from NZn DS children (S.I. = 46.1 +/- 21.5, P less than 0.01). A significant increase in DNA synthesis was obtained after oral administration of zinc sulfate (20 mg/kg/day, for 2 months). The lymphocyte response to PHA appeared to be normal in all patients up to 6 months after the end of the zinc treatment and it became low in half of the patients 22 months after therapy.