A 66 year old patient with diabetes had a necrolytic migratory erythema, weight loss and anaemia. Plasma immunoreactive glucagon (IRG) of 2465 pmoles/l (normal 35 +/- 5 SEM pmoles/l) suggested the existence of a glucagonoma which was confirmed by arteriography and subsequently removed by surgery. Although plasma IRG returned to normal, glucose tolerance and insulin secretion remained pathological. Plasma amino acid levels had been reduced but were corrected by surgery. Pancreatic polypeptide, however, 298 pmoles/l before was still 206 pmoles/l after the operation (normal 12-48 pmoles per litre). Column chromatography of plasma and tumor extracts showed quantitatively important IRG fractions with molecular weights above 9000 daltons, possibly precursors of glucagon. Beside a 50-fold IRG excess, the tumour concentrations of insulin and somatostatin were 4 to 150 times increased. By contrast, pancreatic polypeptide was present in normal amounts. Electron microscopic examination showed atypical A-cell granula and unusual abundance of mitochondria.