1. Incubation of normal and HGPRT-deficient fibroblasts with inosine results in increased PP-ribose-P concentrations. 2. The increased PP-ribose-P concentrations are accompanied by decreased rates of purine synthesis de novo, more marked in normal cells 3. Increased purine nucleotide concentrations during incubation with inosine provide a likely explanation for the inhibition of purine synthesis in normal cells 4. The lack of accelerated purine synthesis in mutant cells under these conditions is not fully explained by consideration of PP-ribose-P and purine nucleotide concentations.