Carbocylic 2′,3′-didehydro-2′,3′-dideoxyguanosine (Carbovir; NSC 614846) is an antiretroviral agent which may be useful in the treatment of AIDS. We have synthesized the 5′-triphosphate of Carbovir and examined its ability to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 184.108.40.206) and other retroviral reverse transcriptases, as well as human DNA polymerases α, β, γ (EC 220.127.116.11) and DNA primase (EC 18.104.22.168). Carbovir triphosphate emerges as a highly selective inhibitor of reverse transcriptases with little, if any, effect on the cellular enzymes. 3′-Azido-2′,3′-dideoxythymidine (AZT) triphosphate and the two dideoxynucleoside triphosphates, ddTTP and ddGTP, inhibited HIV-1 reverse transcriptase to the same degree as Carbovir triphosphate, but were less selective in that they also inhibited DNA polymerases β and γ. We conclude that Carbovir is a highly selective antiretroviral agent. © 1989.