The influence of oligodeoxyribonucleotide probes containing 1-(D-beta-2'-deoxythreo-pentofuranosyl)thymine or 1-(D-beta-2'-deoxy-2'-fluoro-pentofuranosyl)uracil on the ability of the hybrid duplexes to interact with RNase H from E. coli was studied. A kinetic approach was used to measure of the modification effect. The hybrid duplex, prA18/d(TTflU)6TT, was shown not to interact with RNase H, whereas prA18/d(xTTT)6 inhibited the RNase H activity (Ki = 0.67 mkM). The thermostability of the modified duplexes was estimated. The present technique may lead to the use of some modified oligonucleotides as antisences.