Oligoribonucleotides consisting solely of FUrd have been prepared. Such oligoribonucleotides when taken up by cells release FUMP that is converted by cellular kinases into FUTP. FUTP is a substrate for viral and cellular RNA polymerases. We hypothesized that cellular uptake of oligoribonucleotides that contain FUrd into virally infected cells would result in efficient incorporation of FUrd into viral RNA. Viruses that utilize highly structured RNA molecules in their replicative processes may be prone to miscode proteins or be otherwise less efficient when FUrd is incorporated into viral RNA. To test this hypothesis we have prepared four oligomeric compounds that contain FUrd or FdUrd. Compound (1) contains six FdUrd and is a deoxynucleotide. Compound (2) is identical to compound (1) but contains a phosphorothioate backbone. Compound (3) is an oligoribonucleotide containing two FUrd in a 10 nucleotide oligomer. Compound (4) is an oligoribonucleotide containing eight FUrd residues. The oligomeric FUrd and FdUrd compounds (1) - (4) were tested for anti-viral activity against the parvovirus H-1. They all reduced virus yields with compounds (1), (2), and (3) reducing titers by 1.75 +/- 0.25 10-2 and compund (4) reducing titers by 10-3. Addition of deoxythymidine (dT) at 10-5 M reduced the inhibition of compounds (3) and (4) by a factor of 10 suggesting a TS independent mechanism. In addition, compound (4) had a dramatic effect on the morphology of infected or uninfected human kidney cells with or without the added dT. The treated cells assumed a more rounded shape within 24 hours of exposure to the drug. We will further discuss the cytoxic and antiviral effects of these and related compounds.