enzyme patterndirected chemotherapy synergistic interaction of 3deazauridine with dgalactosamine we tested an experimental approach in which the specialized enzymatic pattern characteristic of the tissue of origin of a tumor might be exploited to target and enhance drug selectivity in the present work the dgalactosamineinduced depletion of uridine 5triphosphate primarily a hepatic event was employed to enhance the growth inhibition caused by 3deazauridine as predicted the drug effect was most pronounced in the slower growing well differentiated hepatoma lines where the activities of certain hepatic metabolic pathways and enzymes though decreased were still operative the interactions of dgalactosamine and cytosine arabinoside with 3deazauridine were examined in vitro in four liver tumor cell lines and two nonhepatic lines the effects of dgalactosamine and 3deazauridine on the growth of the morris hepatoma cell lines 3924a 8999sand 8999r were strongly synergistic on the novikoff hepatoma and the nonhepatic cell lines they were only additive the combination of 3deazauridine with cytosine arabinoside gave approximately additive growth inhibition with all cell types without selective toxicity towards the hepatocellular lines results of growthinhibition studies with the combination of dgalactosamine and cytosine arabinoside and with combinations of all three agents are also presented these results are analyzed in the context of the regulation of hepatic pyrimidine nucleotide metabolism and our design of enzyme pattern directed drug selectivity