Several 2′,3′-dideoxynucleosides have proven to be effective against HIV-1 in cell culture. The 2′,3-unsaturated analogues dideoxycytidinene (D4C) and dideoxythymidinene (D4T) are among the most potent and selective inhibitors of HIV-1 replicationin vitro. However, 2′,3′-didehydro-2′,3′-dideoxynucleosides are relatively unstable. A chlorine substituent at the 2′-position increases the stability, and, therefore, some 2′-chloro-2′,3′-didehydro-2′,3′-dideoxynucleosides were synthesized and evaluated for anti-HIV-1 activity.