The synthesis of 10-alkyl analogues of the potent antitumor agent 8,10-dideazaminopterin is described. Alkylation of appropriate alpha-alkyl homoterephthalate esters with 2,4-diamino-6-(bromomethyl)-8-deazapteridine afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters. Ester cleavage and decarboxylation at C-10 were accomplished by heating with sodium cyanide in Me2SO at 170-180 degrees C to afford the 2,4-diamino-10-alkyl-8,10-dideazapteroic acids. The acids were coupled with diethyl glutamate, followed by saponification, to give the 10-alkyl-8,10-dideazaminopterins. The compounds were potent inhibitors of growth in folate-dependent bacteria, Streptococcus faecium and Lactobacillus casei. The 10-methyl and 10-ethyl analogues gave the highest percent increases in life span for mice infected with L1210 leukemia with ILS values of +203 and +235%, respectively.