The antiviral activities of analogs of the double-stranded complex of polyinosinic and polycytidylic acids [poly(I).poly(C)], which is a potent interferon inducer, have been studied. Structural changes that modify the polymer backbone substantially, such as loops or 2' --> 5' phosphodiester bonds, lead to decreased antiviral activity. Unexpectedly, however, the complex of polyinosinic acid and poly(1-vinylcytosine), which is only a much more distantly related analog of poly(I) . poly(C), shows high activity. It is postulated that the high activity is related to the reduction of the charge/mass ratio and to the existence of this complex in an aggregated state; these are two factors that generally enhance the uptake of compo unds by cells.