Maitake (Grifola frondosa) is a popular mushroom in Asia for its tasty flavor and immune-stimulating property. The aim of the study is to investigate the innate immunity augmentation effects of different extracts of mycelia and culture filtrate from G. frondosa in submerged cultures. The hot water extract of mycelia showed the strongest cytokine induction effect as a function of its concentration in human whole blood culture. The most potent fractions of hot water extract, Fr. I and II, were mainly composed of polysaccharides with molecular masses of 43-140 and 13-38 kDa, respectively. These fractions (0.025 mg/mL) showed marked activity in enhancing phagocytosis of human polymorphonuclear neutrophils (PMN). In parallel, the expression of CD11b, an early marker of PMN activation, was also up-regulated dose dependently. This result suggested that complement receptor 3 was primed by these fractions. In addition to activation of phagocytes, these bioactive fractions also increased human peripheral blood natural killer cell cytotoxicity. These results imply that the relatively low molecular mass polysaccharides isolated from mycelia of G. frondosa can enhance innate immunity in vitro and therefore may serve as biological response modifiers.