Nutritional deficiencies are believed to be instrumental in producing reduced immune responses in a variety of animal species. Malnutrition may result in an increase or a decrease in immune functions, depending upon its degree, and also the timing and severity of the nutritional protein deprivation. Our experimental data suggest that there is a significant impairment of cytotoxic activity against K-562 and of the ability of spleen cells to produce interferon in protein-deprived mice in comparison with control mice. Paradoxically accelerated tumor growth after administration of OK-432 or Lentinan was also noted in protein-deficient tumor-bearing mice. In addition, a clinical randomized study of advanced or recurrent gastric cancer patients treated with MMC and FT(MF) with or without lentinan was performed. We recognized excellent end-point results only in the lentinan-treated patients with normal protein levels, while no effect of this agent was seen in patients with low serum protein levels (below 5.9/dl). Aggressive postoperative chemotherapy for cases with distant lymph node metastasis was performed under active nutritional support without any depression of metabolic and immunological states, resulting in a good 5-year survival rate (36.9%).