We examined the effects of low-copper diets on indexes of immune response of 11 healthy men (aged 21-32 y) during a 90-d metabolic suite study. Daily copper intake for the first 24 d, next 42 d, and the last 24 d of the study was 0.66, 0.38, and 2.49 mg, respectively. Feeding the diet with 0.38 mg Cu/d was associated with a significant (P < or = 0.05) decrease in the proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin, Concanavalin A, or pokeweed, and an increase in the percentage of circulating B cells (CD 19+), but had no effect on the concentration of serum interleukin 2 receptor, the percentage of peripheral monocytes, neutrophils, CD3+, CD4+, or CD8+ T cells; or on the neutrophil phagocytic activity. Feeding 2.49 mg Cu/d for 24 d prevented further decreases in the indexes affected by the low-copper diet but did not restore them to the prestudy concentrations, even though plasma copper and ceruloplasmin concentrations were restored to normal.