CVT-E002 (sold commercially as COLD-fX) is a patented, polysaccharide-rich extract of North American ginseng (Panax quinquefolium) with purported beneficial effects on influenza and the common cold, although its mechanism of action is largely unknown. This study was conducted to determine the effects of feeding CVT-E002 versus a ginsenoside-containing extract on systemic and gut-associated immune function. For 7 days, male weanling Sprague-Dawley rats (n=10/group) were fed one of four diets: control, low CVT-E002 (450 mg/kg), high CVT-E002 (900 mg/kg), or ginsenoside (450 mg/kg). Lymphocytes were isolated from spleen, mesenteric lymph nodes and Peyer's patches, and immune cell proportions and cytokine production were measured. IgA-positive cells in the jejunum were also assayed. CVT-E002 consumption (particularly at the higher dose) decreased spleen IL-2 and IFN-gamma production following ConA and/or LPS stimulation for 24 or 48 h (P<0.05). Also, CVT-E002-fed rats had a lower proportion of total CD3+ cells and activated T cells (P<0.05). After 48 h of ConA stimulation, spleen IL-1beta production was higher (P<0.05) for animals fed the high dose CVT-E002, whereas TNF-alpha production did not differ significantly from the control group. Feeding the ginsenoside diet resulted in lower (P<0.05) spleen IL-2 production, but the IFN-gamma, TNF-alpha and IL-1beta response to ConA was not different from control animals at 48 h. A higher proportion of jejunal IgA-positive cells was found in rats fed the ginsenoside diet (P<0.05). In conclusion, feeding CVT-E002 modifies systemic immune responses and appears to affect gut-associated immunity in a manner distinct from that of ginsenoside-containing extracts of North American ginseng.