We studied the effect of varying oxygen supply on the endocrine and exocrine secretions of the isolated perfused porcine pancreas utilizing completely synthetic perfusion medium with and without the addition of erythrocytes. With synthetic medium oxygenated to a Po2 of 500 mmHg, oxygen consumption was constant for flow rates at or above 0.5 ml x min-1 x g-1 (wet weight). Addition of erythrocytes to the medium did not increase oxygen consumption at flow rates above this level. Furthermore, the secretion of fluid, bicarbonate and protein in response to secretin and acetylcholine was not influenced by addition of erythrocytes. Similarly, the secretion of insulin, glucagon, pancreatic polypeptide, and somatostatin in response to arginine and acetylcholine was unchanged; arginine stimulated the secretion of all four peptides, whereas acetylcholine stimulated the secretion of insulin and pancreatic polypeptide and inhibited glucagon and somatostatin secretion. The results indicate that the porcine pancreas is respiring adequately, when perfused with a completely synthetic perfusion medium at flows above about 0.5 ml x min-1 x g-1 and Po2 about 500 mmHg, and that addition of erythrocytes is not necessary for the study of its secretory functions.