In this study we have assessed zinc status and zinc-dependent cell-mediated immune functions (interleukin-2 production by mononuclear cells, natural killer cell lytic activity, and interleukin-1 beta production by mononuclear cells) in adult patients with squamous cell carcinoma of the upper aerodigestive tract at diagnosis and before any therapy was instituted. Inasmuch as significant interactions between zinc, copper, and iron exist, we also assayed the plasma copper level, serum iron level, and total iron-binding capacity in our patients. We recruited 30 cancer subjects and 21 control subjects. On the basis of cellular zinc criteria, we diagnosed a mild deficiency of zinc in 53% of cancer subjects. The plasma zinc level was not decreased in our subjects. A univariate analysis was applied by use of one-way analysis of variance comparing study variables among the three study groups (controls and zinc-deficient and zinc-sufficient cancer patients) and Tukey's multiple comparison test, and we showed that interleukin-2 production and natural killer lytic activity were decreased in zinc-deficient cancer patients. Interleukin-1 beta production (ELISA assay) was increased in both zinc-deficient and zinc-sufficient groups. Plasma copper level was not different, but the iron utilization was decreased in both groups of cancer subjects. We conclude that zinc deficiency and zinc-dependent immunologic dysfunctions are present in more than half of the patients with head and neck cancer in the Detroit area.