To investigate antiherpetic activity, an acidic protein bound polysaccharide (APBP) was isolated from carpophores of Ganoderma lucidum. This brownish APBP was isolated from water soluble substances of the carpophores by activity-guided isolation method. APBP was tested for its antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay in tissue culture. APBP showed potent antiviral activity against HSV-1 and HSV-2 in Vero cells at its 50% effective concentration (EC(50)) of 300 and 440 microg/ml, respectively. APBP had no cytotoxicity on Vero cells at a concentration of 1 x 10(4) microg/ml. APBP exhibited a potent antiviral activity with selectivity index (SI) of more than 22.73. The combined antiherpetic effects of APBP with nucleoside antiherpetic agents, acyclovir (ACV) and vidarabine (ara-A), were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. CI values were in the range 0.47-0.51 for a combination of APBP with ACV, and in the range of 1.02-1.18 for a combination of APBP with ara-A. The combinations of APBP with ACV on HSV-1 and HSV-2 showed potent synergistic effects, and these results suggest that the possibility of developing APBP as a new antiherpetic agent.