Deficiencies in acid excretion during hypercalcemia have been reported, and this defect has been ascribed to a deficiency in ammonia excretion. Because no changes in urine pH and urine flow occurred to explain decreased ammonia excretion, this suggested to us that decreased excretion was secondary to decreased renal ammonia production. To test this hypothesis, we investigated the ability of kidney slices from rats to produce ammonia and glucose and to consume oxygen when incubated in varying concentrations of calcium. High medium concentrations of calcium (3 and 4 mM) decreased kidney slice ammonia-genesis from glutamine and glutamine and kidney slice oxygen consumption while not affecting gluconeogenesis. Based upon our findings, we propose that hypercalcemia decreases urine ammonia excretion by depressing renal ammonia production.