A series of 6-alky 1 -2,4-diaminopyrimidines (compounds 1-5) and 6»inethyiamino-2,4-dia-minopyimidines (compounds 6-12), prepared as nonclassical folate antinmetabolites, were subjected to inhibition study on bovine liver dlhydrofolate reductase. The 2,4-diaminopyrimidine compounds showed IC50’s at lO-7lO-9M, with compound 5 as the most acitve showing comparable activity to that of methotrexate. The triaminopyriinidiiie analogues 6-12 were much less active, with IC50’s ranged between 10-4-10-6M.