In order to evaluate the effect of acute moderate hypercalcemia on both smooth and skeletal muscle function of the human esophagus, 12 subjects were given intravenous calcium chloride in normal saline. Serum calcium increased from a basal value of 9.6 +/- 0.1 mg per dl (mean +/- 1 SEM) to 11.4 +/- 0.2 mg per dl at 90 min after initiation of calcium infusion (P less than 0.01). Both amplitude and Dp/Dt of esophageal contractions decreased significantly in the skeletal muscle segment; however, amplitude and Dp/Dt increased significantly in the smooth muscle segment. Lower esophageal sphincter pressure remained unchanged. Duration of contractions and peristaltic wave speed were unaltered. Possible explanations for the divergent effect of hypercalcemia on the two types of esophageal muscle are discussed.