The possible antiherpetic effect of three polyanions (heparin, chondroitin sulfate and dextran sulfate), as well as one polycation (protamine sulfate) was tested in vitro and in vivo against pseudorabies virus (Suid herpesvirus 1). The in vitro experiments revealed that heparin, dextran sulfate and protamine sulfate significantly reduced the number of lytic plaques. Chondroitin sulfate only caused a decrease in mean plaque size. Experiments in vivo disclosed that heparin injected subcutaneously before the experimental infection, was the only polyanion that protected mice against pseudorabies virus. Protamine sulfate had a paradoxic effect: whereas in vitro it reduced the number of lytic plaques, in vivo it increased the lethality of pseudorabies virus. Chondroitin sulfate and dextran sulfate did not modify the virulence of the virus in mice.