Chondroitin sulfate (CS) is a glycosaminoglycan that is widely present in animals organisms, and it has anti-inflammatory and chondroprotective properties. To examine the effects of CS on the immune system, splenocytes obtained from ovalbumin (OVA)-sensitized BALB/c mice were challenged with OVA in the presence of CS, and cytokine levels in the medium of the cultured cells were measured. CS induced secretion of Th1-type cytokines (IFN-gamma, IL-2, and IL-12) by OVA-sensitized splenocytes but suppressed secretion of Th2-type cytokines (IL-5 and IL-10). Flow cytometric assay showed a significantly higher percentage of helper T cells (CD4(+)CD8(-) cells) among the splenocytes cultured with OVA and CS than with OVA alone. Analysis of the IFN-gamma mRNA level of the splenocytes by the real-time quantitative RT-PCR technique revealed higher levels in the splenocytes cultured with OVA and CS than in the splenocytes cultured with OVA alone. This is the first demonstration that CS inhibits antigen-induced IgE production through induction of cytokine secretion by Th1 cells, and this finding suggests a potential use of CS in preventing IgE-mediated allergy.