Among different neutral polysaccharides from natural sources, scleroglucan from Sclerotium glucanicum significantly inhibits the replication of herpes simplex virus type 1 on Vero cells. Scleroglucan belongs to a class of exopolymers, expressed by members of genus Sclerotium and consists of a linear beta-1,3-linked glucopyranose with side chains of single glucopyranose residues linked through beta-1,6 glycosidic bonds. The effective antiviral concentration of this polysaccharide is far from the cytotoxicity threshold and consequently this natural product possesses a good selectivity index. Results obtained in experiments carried out in order to clarify the mechanism of action of this carbohydrate indicate that the block of infection occurs during the very early phases of the viral mutliplication cycle since the highest inhibitory effect took place when it was added during the attachment step. The antiviral effect of scleroglucan seems to be related to its binding with membrane glycoproteins of HSV-1 particles which impedes the complex interactions of the virus with the cell plasma membrane.