A number of oligodeoxynucleotides containing thymine bases linked to the deoxyribose in the α-configuration have been synthesized. In view of the possible activity of α-origomers as antisense compounds against HIV replication, the effects of α-thymidylate oligomers (α-dTn, n=1-1-16) in a poly (A)-directed HIV reverse transcriptase (RT) reaction were investigated. No priming activity could be detected with the α-dT oligomers at concentrations up to 100 μM. However, in the presence of the natural β-dT12-18 primer, 50% inhibition of RT activity was achieved at a concentration of about 1 μM with the α-dT oligomers containing ≥ 10 monomer units. The kinetics of RT inhibition by the α-decamer was found to be competitive with respect to the natural primer, β-dT10.