Two water-soluble derivatives, sulfated and carboxymethylated Ganoderma lucidem polysaccharides, coded as S-GL and CM-GL, were prepared using derivatization of water-insoluble polysaccharides (GL-IV-I) extracted from the fruit body of G. lucidem . The degree of substitution (DS) of S-GL and CM-GL was 0.94 and 1.09, respectively. The weight-average molecular mass (Mw) of GL-IV-I, S-GL, and CM-GL was determined with light scattering to be 13.3x10(4), 10.1x10(4), and 6.3x10(4), respectively. S-GL and CM-GL inhibited the in vitro proliferation of Sarcoma 180 (S-180) tumor cells in a dose-dependent manner, with an IC50 value of 26 and 38 microg/mL, respectively. They also inhibited the growth of S-180 solid tumors implanted in BALB/c mice, with low toxicity to the animals. Flow cytometric studies revealed that treatment of S-GL and CM-GL with S-180 tumor cells could mediate the cell-cycle arrest in the G2/M phase. The expression of Bax increased, and the expression of Bcl-2 decreased dramatically, as shown by immuno-histochemical staining of S-180 tumor tissue excised from the animals. The sulfated and carboxmethylated groups in the polysaccharides played an important part in enhancing their antitumor activities, leading to the potential to be developed into antitumor drugs.