To study the effect of zinc on the sensitivity of lymphocytes from aged people to prostaglandin E2 (PGE2), ZnCl2 was added to cultures of peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA). Mononuclear cells from 11 aged (greater than 65 years old) and 9 control (less than 36 years old) subjects were cultured with PHA and proliferation was measured 72 hr later by the uptake of [3H]thymidine. Lymphocytes from the aged group, whose mean plasma zinc concentration was significantly lower than that of the control group (68 +/- 6 micrograms/dl and 85 +/- 4 micrograms/dl, respectively), showed a decreased proliferation of lymphocytes and an increased sensitivity to the antiproliferative effect of PGE2. The addition of zinc to cultures increased proliferation of cultured cells in both groups, especially in the aged group. Our data indicate that zinc deficiency can act as a causal factor for T-lymphocyte dysfunction in elderly people.