During the study of eight patients with hypocalcemia of varying etiology an inverse relationship between serum calcium concentration and serum lactic dehydrogenase activity (SLDH) was noted. Initial serum calcium concentrations ranged from 3.7 to 7.1 mg per 100 ml and were associated with elevated SLDH activity of 151 to 400 U. In all patients the SLDH returned to the normal range as the serum calcium concentration rose with treatment. This occurred regardless of the type of therapy, which included parathyroid extract, vitamin D and oral calcium salts. The addition of calcium to hypocalcemic serum in vitro failed to alter the elevated SLDH activity. Studies of serum LDH isoenzymes from two patients indicated that the elevated LDH activity was localized to bands 1, 2, and 3 in approximately equal distribution. While the physiologic significance of these observations remains to be elucidated, an inverse relationship between serum calcium and SLDH has been demonstrated and warrants consideration in the evaluation of elevated SLDH levels in clinical situations.