Interactive combinations of altered zinc and thyroid states were studied in rats to assess pathophysiologic effects. Clinical signs of zinc deficiency or thyroid alteration were limited to effects on growth rate. Changes in organ and glandular weights and serum thyrotropin levels reflected changes in serum thyroid hormone concentrations. Significantly (probability less than .001), zinc-deficient rats had enhanced hepatic thyroxine-5'-monodeiodinase activity. In addition, the zinc-deficient state was found to be protective against thiouracil-induced suppression of the microsomal-monooxygenase and thyroxine-5'-monodeiodinase enzyme complex. This protective effect was evident by greater thyroxine-5'-monodeiodinase and reduced nicotinamide-adenine dinucleotide phosphate cytochrome c reductase activities, as well as cytochrome P-450 content, in zinc-deficient/thiouracil-treated animals. Thus, the enzyme complex had increased triiodothyronine-generating capacity in conditions of zinc deficiency, which may be important because of the greater biological reactivity of triiodothyronine. Primary zinc deficiency conditions of the magnitude seen in this study and in this-age rat did not appear to alter serum thyroid hormone levels or organ/glandular function. However, concurrent zinc deficiency and altered thyroid status did change thyroid hormone response and disposition, which may be important to populations at risk because of thyroid dysfunctional states.