A method is described for the in vivo surgical removal of all Peyer's patches from the small intestine and caecum of the rat. Over two postoperative months, this procedure had no apparent morphological effects on the small intestine or intraepithelial lymphocyte numbers, nor were the numbers of IgA producing cells in the small intestine or serum immunoglobulin levels permanently influenced. However, circulating specific antibody to human serum albumin was significantly elevated in animals without Peyer's patches 3 weeks after surgery, in comparison with a sham operated group of animals. Subsequent intestinal immunization in animals without Peyer's patches with a lipid-conjugated human serum albumin resulted in a diminished primary but a comparatively normal secondary systemic antibody response to this antigen.