The possible role of circulating immune complexes (IC) in the production gastrointestinal lesions was studied in rabbits with chronic serum sickness (CSS) induced by multiple daily injections of bovine serum albumin (BSA). All rabbits generating a marked antibody response developed IC glomerulonephritis. In approximately 50% of these rabbits granular deposits of BSA, rabbit IgG, and C3 were also found in the gastrointestinal tract. The immune deposits in the gastrointestinal tract were mainly present in the vessel walls, close to the intestinal glands and the surface epithelium, and between the smooth muscle cells. This was accompanied by slight to moderate edema of the mucosa and the submucosa and mild infiltration of inflammatory cells. Electron-densedeposits were found in a pattern corresponding to that observed for BSA, rabbit IgG, and C3. Degranulated neutrophils, basophils, and mast cells were noticed in the interstitium. The presence in the same areas of granular deposits of BSA, IgG, and C3, corresponding to electron-dense deposits, suggests that the deposits contain BSA-anti-BSA complexes. These findings show that in rabbits with CSS circulating IC may localize and induce injury in the gastrointestinal tract.