Phosphoribosylpyrophosphate (PRPP) synthetase activity and the intracellular concentration of PRPP were assayed in erythrocytes from patients with primary hyperuricemia and primary metabolic gout. Sensitivity of the enzyme to feed-back inhibition by adenosine diphosphate (ADP), guanosine diphosphate (GDP), and 2,3-diphosphoglycerate (2,3-DPG) was determined. All patients with gout and four of ten patients with hyperuricemia were taking allopurinol during the study. Mean PRPP synthetase activity in erythrocytes from hyperuricemic and gouty patients was similar to that in normal subjects, and feedback inhibition by ADP, GDP, and 2,3-DPG was intact. The concentration of PRPP in erythrocytes was higher in normal females than in normal males, higher in normal subjects than in gouty patients, and lower in hyperuricemic patients taking allopurinol than in those hyperuricemic patients not taking this drug. The difference in intracellular levels of PRPP in erythrocytes in gout versus hyperuricemic patients was not significant. The significance of these findings is discussed in relation to the regulation of PRPP synthetase and in the important regulatory role of PRPP in purine metabolism.