Copper deficiency is associated with a selective atrophy of the pancreas. Copper deficiency is also associated with hepatic iron retention. In the past, we have shown that the reduction of dietary iron prevented the pathologies of the pancreas in copper-deficient rats. The present study was designed to determine whether the reduction of dietary iron in copperdeficient rats would alleviate functional disturbances of the endocrine and exocrine pancreas. Weanling male rats were fed a copper-deficient (0.6 g Cu/g) or adequate (6.0 gCu/g) diet containing either adequate (50 g Fe/g) or low (17 g Fe/g) iron for 4 weeks. Rats were killed following an overnight fast. Insulin, amylase and lipase were measured in pancreatic tissue. Copper-deficient rats fed the adequate-iron diet exhibited extremely high levels of insulin but low activity of amylase and lipase. Once the intake of dietary iron was reduced, levels of pancreatic insulin and activity of digestive enzymes returned to normal. Lowering intake of dietary iron resulted in reduction of liver and pancreas iron but caused an expected increase in copper concentrations. Low iron was also associated with reduction of lipid peroxidation. It is suggested that reduction of free radicals was responsible for restoring the ability of the endocrine pancreas to release insulin, which in turn stimulated the exocrine pancreas to synthesize digestive enzymes.