Oligodeoxynucleotides covalently linked to an acridine derivative were targeted to part of the 3'-terminal sequence which is common to the eight RNAs of type A influenza viruses. The cytopathic effect of the virus on MDCK cells in culture was strongly decreased by a heptanucleotide covalently attached to the acridine ring. Control experiments using other oligonucleotide sequences showed that the effect was specific for the complementary sequence of the 3'-terminal region of the viral RNAs. The RNA transcriptase reaction of a type A virus was also selectively inhibited in vitro by the heptanucleotide-acridine conjugate. A type B influenza virus was used as a control. The common sequence at the 3' end of its eight viral RNAs is different from that of type A viruses. Three mismatches were expected with the heptanucleotide which was fully complementary to type A viral RNAs. This heptanucleotide had no effect on the cytopathic effect of a type B influenza virus. These results demonstrate that viral RNAs are specific targets for the oligonucleotide-acridine conjugate that inhibits the cytopathic effect of type A influenza viruses.