In view of recent developments, the structural determinants of the interferon inducing activity of polynucleotides have been (re)evaluated. To induce interferon, the polynucleotide should be sufficiently large and double-stranded, although not necessarily double-stranded over its whole length. It should be sufficiently stable to both thermal denaturation and hydrolysis by nucleases. It should also contain a particular steric conformation. This conformation is most regularly ensured by the presence of 2'-hydroxyl in the ribose moieties and intact purine-pyrimidine base pairs in the interior of the double helix. Other biologic activities of polynucleotides, such as anti-complement activity and inhibition of reverse transcriptase (RNA-directed DNA polymerase) activity, depend on structural requirements which are rather antagonistic to those governing the interferon response.