OBJECTIVE Metabolism of zinc was studied by administering radioactive zinc (Zn65), and by performing metabolic balance studies in eight patients with exocrine pancreatic insufficiency and eighteen control subjects. METHODS Retention of radioactive zinc was measured by total body counter, and its urinary and fecal excretion by gamma scintillation counter. Metabolic balance studies were carried out by measuring dietary zinc intake as well as fecal and urinary excretion of zinc by atomic absorption spectrophotometry in this group of patients. RESULTS These studies revealed a 50% reduction in intestinal absorption of Zn65 in patients with exocrine pancreatic insufficiency as compared to alcoholic and non-alcoholic control subjects. In addition, there was a 2 to 4 fold increase (p<0.05) in urinary excretion of zinc in subjects with pancreatic disease. In pancreatic insufficiency, reduced zinc absorption and increased urinary zinc excretion were balanced by lower (p<0.05) endogenous excretion of zinc as evidenced by reduced excretion of Zn65 in feces during the second 4-day period. The mean biological half-life of Zn65 tended to be lower in patients with pancreatic insufficiency as compared to alcoholic control subjects, however the difference did not reach statistical significance. CONCLUSIONS These observations indicate marked alterations in zinc metabolism in patients with advanced chronic pancreatic disease and provide greater insight into development of zinc deficiency in this group of patients.