The immunomodulatory effect of fermented non-salty soybean powder (NSBP) was investigated in C3H/HeN mice. The number of splenic CD11b(+), CD49b(+), and interferon (IFN)-γ(+)CD4(+) cells increased significantly, while that of interleukin (IL)-4(+)CD4(+) and CD19(+) cells decreased significantly in cultures containing NSBP. Similarly, in the spleen and Peyer's patches of mice fed a diet containing NSBP, the number of IL-12(+)CD11b(+), CD49b(+), and IFN-γ(+)CD4(+) cells increased noticeably, whereas the number of splenic IL-4(+)CD4(+) and CD19b(+) cells was lower compared to mice fed an NSBP-free diet. Superoxide production by peritoneal macrophages was significantly higher in mice fed an NSBP-containing diet. Both intestinal total IgA and serum total IgG levels declined in mice fed the NSBP-containing diet. Microarray analysis of mRNAs extracted from Peyer's patch cells of mice fed the NSBP-containing diet indicated an increase in the expression of several genes related to cellular immune responses, while the expression of genes related to immunoglobulin production decreased. These results indicate that NSBP stimulates the cellular immune response, but suppresses the acquired humoral immune response in C3H/HeN mice.