Serum concentrations of ionized calcium, parathyroid hormone, and calcitonin were measured during zinc infusion in patients of short stature (n = 15); those with insulin-dependent diabetes mellitus (n = 13); and age-matched controls (n = 10). The increase in serum zinc concentrations after zinc infusion resulted in a decrease in the serum calcitonin concentrations but not in concentrations of ionized calcium and parathyroid hormone. A significant negative correlation was obtained between body zinc clearances and decreases in serum calcitonin levels at 60 minutes after the infusion of zinc. Thus, we found a relationship between infusion of zinc and the regulation of calcitonin secretion. We propose that an increase in the serum zinc pool plays a definite role in inhibiting calcitonin secretion from thyroid tissue.