PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells.