Rats were immunized by intraperitoneal injection of ovalbumin (egg albumin) emulsified in Freund's incomplete adjuvant, and then the effect of an intravenous challenge with ovalbumin on salicylic acid absorption from the small intestine was examined by means of an in situ recirculation technique. The disappearance of salicylic acid from the luminal solution was significantly decreased in rats treated with ovalbumin compared with control groups treated with saline. The decreased absorption of salicylic acid in ovalbumin-immunized rats was related to the anti-ovalbumin antibody responses examined by passive cutaneous anaphylactic reactions. On the other hand, the decreased absorption of salicylic acid was not found in ovalbumin-immunized rats challenged intravenously with bovine gamma-globulin. Similar results were also noted in rats immunized via the footpads with ovalbumin. However, no significant change was observed in the intestinal absorption of salicylic acid in normal (nonimmunized) rats challenged intravenously with ovalbumin. Furthermore, intestinal absorption of sulfadimethoxine and sulfanilamide was significantly decreased during systemic anaphylaxis, whereas no change was observed in the absorption of sulfisoxazole, quinine, sulfanilic acid, and phenolsulfonphthalein. This suggests that the intestinal absorption of rapidly absorbed drugs, including salicylic acid, is more sensitive to systemic anaphylaxis than that of poorly absorbed drugs.