The effect of local and systemic calcium administration was tested on the pancreas of cat and guinea pig. After 3 h of local calcium infusion (0.6 mmol/kg x h) via the splenic artery of the cat hemorrhagic pancreatitis could be shown. Control animals treated with potassium (1.1 mmol/kg x h) or 0.9% NaCl alone showed no morphological change in the pancreas. Intravenous administration of calcium (0.6 mmol/kg x h) led to a 1.8-fold increase in serum ionized calcium levels in the cat and a 1.6-fold increase in levels in the guinea pig. The cat showed necrosis of acinar and ductal cells throughout the gland at 12 h. In the guinea pig, acinar cell vacuolisation and cell necrosis started at 3 h, and at 9 h degeneration of entire acini, hydropic swelling and degeneration of ductal cells, and perivascular leukocytic infiltration was present. In both species, a significant increase in the number of intraductal precipitates and a significant increase in urinary amylase output was present in calcium treated animals. The findings suggest that hypercalcemia has a deleterious effect on the pancreas that causes acinar and ductal cell necrosis and eventually pancreatitis.