Antitumor activity of twenty seven 6-alkyl disulfide derivatives of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were examined in the system of murine L-1210 leukemia. When given by intraperitoneal administration, maximum increase in life span produced by iso-pentyl (75%) and heptyl (68%) disulfides of 6-MP and sec-butyl (83%), pentyl (78%), and naphthyryl (90%) disulfides of 6-TG were higher than that of parent compounds (6-MP: 53%, 6-TG: 64%). Compounds with higher therapeutic ratio than respective parent compound were decyl and naphthyryl disulfide derivatives of 6-MP and almost all the derivatives of 6-TG tested (propyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, decyl, benzyl, and naphthyryl disulfides of 6-TG). Among them, decyl derivatives of both 6-MP and 6-TG showed the highest therapeutic ratio as high as 50 and 48, while those of parent compounds were 6.2 and 5.0, respectively. The improvement of therapeutic effect by the modification to decyl disulfide of 6-MP was demonstrated inthe L-1210 system, but it was not found in the Sarcoma-180 system reported previously. By oral administration, these derivatives were active against the leukemia but they were not superior to the parent compounds.