The effects of caps, dinucleotides, oligonucleotides and polynucleotides on influenza virus RNA polymerase activity have been investigated. The results show that both methyl groups in a cap are necessary for optimal stimulation of polymerase activity. Both m7G(5')ppp(5')Am and ApG stimulated the influenza RNA polymerase activity and seemed to interact at different sites. Out of the 16 homopolynucleotides tested, seven inhibited influenza RNA polymerase by 50% at 2-10 micrograms/ml. Poly(G) gave a 90% reduction of influenza virus plaque formation at 10 micrograms/ml. An oligodeoxyribonucleotide complementary to the 12 terminal nucleotides of the 3' end of influenza virus RNA was synthesized. This oligonucleotide did not selectively inhibit influenza RNA polymerase.