The effects of azaserine, thioguanine and 6-mercaptopurine on the metabolism of 4-aminopyrazolopyrimidine- 14C and of 4-aminopyrazolopyrimidine on the metabolism of thioguanine- 14C and of 6-mercaptopurine- 14C have been studied in Ehrlich ascites carcinoma and ascites sarcoma-180. Azaserine, thioguanine and 6-mercaptopurine not only enhanced the inhibition of tumor growth by 4-aminopyrazolopyrimidine, but also increased the amount of incorporation of the analog into tumor polynucleotides. Enhancement of the size of the pool of 4-aminopyrazolopyrimidine mononucloetides was evident during dual treatment with azaserine and thioguanine. The amount of incorporation of radioactivity from labeled 6-mercaptopurine into polynucleotides was decreased by 4-aminopyrazolopyrimidine, while little change in the size of the labeled mononucleotide pool was evident. The therapeutic effectiveness of thioguanine was increased by the co-administration of 4-aminopyrazolopyrimidine and the amount of incorporation of thioguanine into nucleic acids was somewhat increased by 4-aminopyrazolopyrimidine. These results are discussed with respect to present hypotheses concerning the anabolic conversion of purine analogs into their active derivatives.