Male Sprague-Dawley rats were fed a zinc-deficient diet to study its effects on the hypothalamic-pituitary-thyroid axis. As zinc-deficient animals fail to gain weight, they were compared to pair-fed growth restricted animals as well as ad libitum fed controls. The growth velocity curves were superimposable for the zinc-deficient animals and the pair-fed controls; both were markedly reduced compared to the ad libitum controls. Both the zinc-deficient and the pair-fed controls had lower triiodothyronine (T3) and thyroxine levels compared to the ad libitum controls. In addition T3 values were lower in the zinc-deficient animals compared to the pair-fed controls (P < 0.05). Hypothalamic thyrotrophin-releasing hormone content was decreased in the zinc-deficient rats (162 +/- 32 pg/ml) compared to the ad libitum controls (305 +/- 102; P < 0.01). The 125I thyroidal uptakes were not significantly different between the zinc-deficient and the pair-fed controls. Zinc deficiency lowers T3 more than comparable caloric restriction; this suggests that zinc deficiency may impair extrathyroidal production of T3.