Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituents, which indicate that hydrophobic bonding is occurring, possibly in the same area adjacent to the active site.