A sulfated polysaccharide fraction was isolated from the hot water extract of the green alga Caulerpa racemosa and designated HWE. This polymer, which contained galactose, glucose, arabinose and xylose as the major component sugars, had [alpha](D)(30) + 46.2 degrees in water and contained 9% sulfate hemiester groups. Sugar linkage analysis indicates that HWE was branched and mainly contained 1,3- and 1,3,6-linked galactose, 1,3,4-linked arabinose, 1,4-linked glucose and terminal- and 1,4-linked xylose residues. Sulfation was deduced from infrared spectroscopy and methylation analysis to occur on O-6 of galactose and O-3 of arabinose. The native polysaccharide could be fractionated by size exclusion chromatography into two overlapping fractions and the major fraction has a hydrodynamic volume similar to that of 70 kDa dextran. HWE was a selective inhibitor of reference strains and TK(-) acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells, with antiviral effective concentration 50% (EC(50)) values in the range of 2.2-4.2 microg/ml and lacking cytotoxic effects. Furthermore, HWE did not exhibit anticoagulant properties at concentrations near the EC(50).