Some intercalating and nonintercalating drugs have been tested as inhibitorrs on the DNA synthesis reaction catalyzed by avian myeloblastosis virus (AMV) reverse transcriptase, in the presence of polyriboadenylic acid (poly(rA)) and poly(2'-fluoro-2'-deoxyadenylic acid) (poly(dAfl)) as templates. In both cases, the inhibition was higher with the intercalating drug ethidium bromide than with the nonintercalating analog tetramethyl ethidium bromide. Ethidium bromide inhibited more efficiently the poly(rA)- than the poly(dAfl)-directed reverse transcriptase reaction; in the latter case, the inhibition was non-competitive in relation to TTP. On the other hand, the reaction catalyzed in the presence of the 2'-fluorinated polynucleotide as template was inhibited to a higher extent by other nonintercalating drugs, berenil, netropsin, and distamycin. The inhibitions of both reactions by dideoxy TTP, novobiocin and HPA-23 are also discussed.92171177