A sulfated galactan (FG) was isolated from the green alga, Codium fragile. Chemical analysis revealed that FG mainly consisted of D-galactose with pyruvic acid (12.3%) and sulfate (11.0%). Methylation and NMR analyses showed that FG was composed of -->3)-beta-D-Galp-(1-->, beta-D-Galp-(1--> and -->3,6)-beta-D-Galp-(1--> residue. In addition, pyruvic acid was suggested to be present as (1'-carboxy)-ethylidene cyclic ketal at O-3 and O-4 of non-reducing terminal galactose residues, whereas sulfate was substituted at O-4 of other galactose residues. When the antiviral potency of FG was evaluated, it inhibited the replication of herpes simplex virus type 2 (HSV-2), and the mechanism of action was suggested to be interference in the early steps such as virus adsorption to and penetration into host cells. Furthermore, it was shown that FG directly reduced virus infection rates. In a genital infection model using HSV-2-infected mice, FG improved mortality and lesion scores and reduced virus yields by intravaginal administration. These results suggest that FG might be a potent candidate as a prophylactic agent for HSV-2 infection.