Carbocyclic-2 ,3 -didehydro-2 ,3 -dideoxyguanosine is the parent compound in a series of 6-substituted-2-amino purine carbocyclic nucleosides (called carbovir, CVR) that are potent and selective inhibitors of human immunodeficiency virus [Vince et al., BBRC 156: 1046, 1988; Vince and Hua, US patents 4,916,224, 4,931,559, 4,950,758, (1990)].We have identified the active CVR enantiomer, characterized its metabolism, identified its active form (CVR-triphosphate) as an inhibitor of reverse transcriptase, and demonstrated its potent synergy with AZT. The 6-alkylamino and 6-alkoxy derivatives were also active against against HIV. The 6-substituted CVR's are metabolized directly to the monophosphates and are subsequently converted to CVR-triphosphate via of CVR-monophosphate. The adenosine deaminase inhibitor, EHNA, had no effect on anti-HIV activity of these compounds, while the adenylic acid deaminase inhibitor, 2-deoxycoformycin, inhibited antiviral activity. The 6-substituted CVR, 1592, a prodrug of CVR-monophosphate, has recently been reported as a clinically active candidate for the treatment of AIDS.