The objective of this work is the discovery of 2',3'-dideoxynucleosides (DDO) which are superior to known inhibitors of the HTLV-III virus. DDO-5-azacytidine was active but somewhat more toxic than DDO-C. The 5-fluoro analog of DDO-C was just as effective and potent as the parent compound in protecting HTLV-III infected cells. However, the 5-bromo and 5-methyl analogs were ineffective. DDO-cyclopentenyl isosteres (neplanocin analogs) proved to be inactive and nontoxic.