A number of oligodeoxynucleotides containing thymine bases linked to the deoxyribose in the -configuration have been synthesized. In view of the possible activity of -origomers as antisense compounds against HIV replication, the effects of -thymidylate oligomers (-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 -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 -dT oligomers containing ≥ 10 monomer units. The kinetics of RT inhibition by the -decamer was found to be competitive with respect to the natural primer, β-dT10.