Immunosuppressive effects of carrageenan, a high-molecularweight polysaccharide, on antibody and T cell responses have been previously demonstrated. However, its effect on anaphylaxis is unknown. Our objectives were to test carrageenanmediated oral tolerance induction in young mice subsequently sensitized to a common cow's milk antigen. C3H/HeJ mice were fed or not -carrageenan (0.5 g/L) and/or 0.01 mg/mL -lactoglobulin (BLG) for 5 d before oral sensitization with BLG and cholera toxin. Subsequently, the mice were challenged with BLG and symptom scores of anaphylaxis were recorded. Mesenteric lymph node cells, spleen cells, Peyer's patches cells, intraepithelial lymphocytes, and lamina propria lymphocytes were isolated and stimulated in vitro with BLG, IL-2, or left unstimulated. BLG-specific IgG, IgG 1 , and IgG 2a antibodies were measured. Pretreatment with carrageenan and BLG, but not pretreatment with either carrageenan or BLG alone or omission of pretreatment, diminished significantly the number of anaphylactic mice after BLG challenge (6.3% versus 53% in mice without pretreatment, p ϭ 0.006). Mesenteric lymph nodes and spleen cells from pretreated mice proliferated less in presence of BLG or IL-2 than cells from sensitized control mice. Antigen-specific antibody production and passive cutaneous anaphylaxis was not suppressed by carrageenan and BLG pretreatment. In conclusion, carrageenan administered to young mice in conjunction with low doses of allergen before sensitization efficiently prevents anaphylaxis. During infancy, large amounts of potentially harmful food antigens are ingested in large quantities and, in most infants, oral tolerance is naturally acquired. Animal studies have revealed that early oral exposure to low amounts of antigen tend to promote sensitization, whereas large amounts favor tolerance induction (1). In human infants it is accepted, that potential food allergens should be completely avoided during the first months of life in infants at risk for allergy. However, these measures are only partially efficient in atopic individuals (2). Development of further strategies favoring induction of earlylife antigen-specific tolerance are strongly needed.Carrageenan is a high-molecular-weight galactose-based polysaccharide. When ingested it is found mostly undegraded in the gut submucosa (3), where it is taken up and cleared by macrophages (4). Although large amounts of oral carrageenan induce colitis (5, 6), small quantities do not appear to be toxic for the gut mucosa (3). Studies in rats have demonstrated an adjuvant effect similar to alum when carrageenan was given with ovalbumin by systemic route, but abrogation of the PCA response when given orally (7). Diminished cellular immune response mediated by carrageenan has also been demonstrated in other models. Bash and Vago fed rats with carrageenan and observed a strongly diminished cellular response in spleen cells and mesenteric lymph nodes cells (8). Rumjanek and Brent showed that intraperitoneal carrageenan suppressed T cell activity ...