After the infusion of fructose, 0.25 g/kg body weight, blood uric acid levels were significantly increased above the mean basal value in five patients with glycogen storage disease (GSD), type I (P less than 0.02-P less than 0.05). The mean fasting blood inorganic phosphate (Pi) level in the patients was 3.9 +/- 0.3 mg/100 ml and was significantly lower than the mean Pi value of 4.8 +/- 0.3 mg/100 ml of the control subjects (P less than 0.05). Blood Pi levels were significantly lower in the patients than in the control subjects at varying times after the administration of fructose (P less than 0.005-P less than 0.05). Uric acid excretion did not increase significantly in the patients after fructose was given. In contrast to normal children, the mean peak blood uric level in the patients increased significantly after the administration of glucagon (P less than 0.001). In both patients (P less than 0.005) and control subjects (P less than 0.05), mean blood Pi concentrations decreased significantly after the administration of glucagon; however, the blood Pi concentrations in the patients were significantly lower than in the control subjects. Uric acid excretion increased after glucagon administration in both patients and control subjects, but the differences in uric acid excretion between the two groups were not significant. The data in our patients after fructose and glucagon administration suggest that hyperuricemia in GSD results from enhanced nucleotide catabolism. The concentrations of hepatic Pi and ATP may be low in patients with GSD; hepatic Pi and ATP content would therefore be further diminished by the administration of fructose and glucagon. By a mechanism similar to that of fructose-induced hyperuricemia, diminished hepatic Pi and ATP content might increase the breakdown of adenine nucleotides with resultant hyperuricemia.