Synthetic oligodeoxynucleotides that are covalently linked at their 3' end to an acridine derivative and are complementary to the repeated sequence UUAAAU-UAAAUUAAA adjacent to the ribosome binding site of the gene 32-encoded mRNA from phage T4 have been used to regulate the synthesis of gene 32-encoded protein in vitro. These modified, synthetic oligonucleotides specifically block the translation of gene 32-encoded mRNA with a higher efficiency than the homologous unsubstituted oligonucleotides. The inhibition produced by these short "anti-messengers" is due to the formation of specific mRNA-oligodeoxynucleotide hybrids that are stabilized by the intercalation of the acridine ring in the RNADNA duplex.