A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was found to have antiviral activity against respiratory syncytial virus (RSV) in the 2-10 microM range in plaque reduction assays and cytopathic-effect-inhibition assays. The material was also virucidal. The 50% effective concentration (EC50) for virucidal activity was 28 microM. Experiments were done to determine the mode(s) of RSV inhibition by SP-303. Interferon was not induced. SP-303 did not inhibit attachment at antiviral concentrations. However, the EC50 for inhibition of virus penetration by SP-303 was 0.48 +/- 0.19 microM. These data suggest that abolition of RSV penetration into host cells is one mechanism whereby SP-303 inhibits RSV replication.