A series of 5'-deoxy-5-fluoropyrimidine nucleosides has been prepared and evaluated against sarcoma 180 tumor in mice. 5'-Deoxy-5-fluorouridine (5) was prepared from 5-fluorouridine (1) by isopropylidination and iodination, followed by reduction and deprotection. The D-lyxo isomer 13 was prepared from 5 by treatment of the 2',3'-dimesyl intermediate 14 with water. The D-arabino isomer 7 was prepared via the 2,2'-anhydro intermediate 8. Treatment of the 5'-iodo compound with sodium methoxide induced elimination in preference to anhydro formation to give the 4',5'-unsaturated compound 11. Hydrogenation of 11 followed by deprotection gave the L-lyxo isomer 10. 5'-Deoxy-5-fluorocytidine (16) was also synthesized via reduction of a 5'-iodo intermediate, 17, and was converted into the D-arabino isomer 20 via the 2,2'-anhydro intermediate 19. Reaction of 16 with methanesulfonyl chloride produced the 3'-O-mesyl-2,2'-anhydronucleoside 21, which on treatment with sodium hydroxide yielded the lyxo-epoxide 22. 5'-Deoxy-5-fluorouridine (5) was active against sarcoma 180 tumor over a wide dose range following intraperitoneal administration. The cytidine analogue 16 showed activity similar to that for 5, and the anhydronucleoside 19 was also active in this system, but the antitumor effect was less than that seen with 5 or 16. The other compounds in this series were all inactive against sarcoma 180 at the doses tested.