The herpes virus inhibitory effect of five extracts from the Bulgarian medicinal plant Geranium sanguineum L. (Geraniaceae) was investigated. The water extract (WE) from the aerial roots of the plant was the least toxic for cell cultures and inhibited significantly the replication of herpes simplex virus type 1 and type 2 (EC50 = 3.6-6.2 microg/ml) as shown by the reduction of virus induced cytopathogenic effect (CPE) and the protection of cells in MTT assay. The inhibition was dose-related, strain-specific and depended on virus inoculum. In higher concentrations (MIC90 = 120 microg/ml) the preparation exhibited strong extracellular virus inactivating activity. The presence of WE throughout the whole replicative cycle was necessary for the full expression of the antiviral effect. In a preliminary experiment in albino guinea pigs the extract delayed the development of herpetic vesicles following primary infection with HSV-1, strain Kupka. Phytochemical investigation of the plant preparation revealed the presence of flavonoids, catechins, a polyphenolic acid and condensed tannins. The inhibitory effect of the extract on herpes simplex virus replication is related to the rich content of polyphenol compounds.