In ureotelic species, such as the rat, adaptive changes in metabolic flux and enzyme levels occur in the purine metabolic pathway when cells are rapidly growing. This is observed in both regenerating liver and in malignant tissues. The enzymes P-Rib-PP amidotransferase and IMP dehydrogenase increase in activity in both situations. The level of purine biosynthesis is much higher in uricotelic species, such as the chick, when compared to ureotelic animals. By treating immature roosters with the hormone beta-estradiol, it is possible to induce rapid liver growth, allowing comparison of the regulation of purine biosynthesis and interconversion in high metabolic rate cells with different roles for purine metabolism. The tissue activities of P-Rib-PP amidotransferase, xanthine dehydrogenase, adenylosuccinate synthetase and lyase, AMP deaminase, IMP dehydrogenase, and GMP synthetase did not rise in livers from estradiol-treated chicks, as compared to controls. However, the rate of de novo purine synthesis triples and the intracellular level of P-Rib-PP doubles within 24 h of treatment. The biosynthesis of GMP is elevated at 12 and 24 h, but the levels of soluble nucleotide pools do not change. These data indicate that regulation of the de novo purine pathway in uricotelic species in a high metabolic situation is at the level of substrate availability (P-Rib-PP) and not due to changes in enzyme level or to feedback inhibition.