Serum immunoglobulin alterations were characterized in 20 patients with chronic inflammatory bowel disease (CIBD) undergoing bowel resection and in 11 control subjects undergoing intra abdominal operations. Serum immunoglobulin M (IgM) values became elevated during the 2nd week in both groups with individual serum IgM concentrations reaching as high as 9 times preoperative values. The IgM increment, which was 19 S polyclonal immunoglobulin, was significantly greater in the CIBD group than in controls. Because of a recent suggestion that this IgM rise might be related to the pathogenesis of CIBD, the affinity of this IgM for colon was studied in two ways. Serum anticolon antibody titers did not change after surgery nor did IgM, isolated from serum after surgery and labeled with 125I, bind to homogenates of normal or CIBD colon. Titers of heterophile antibody and antibodies directed against Escherichia coli, Bacteroides, and blood group antigens increased in many patients. In most instances, these increments were shown to be antibody of the IgM class by reduction with 2 mercaptoethanol. These data indicate that the IgM changes after abdominal surgery are not specific for CIBD patients, do not represent antibody directed against colon antigens, and include increased titers of several IgM antibodies. These findings might be explained by a response to bacterial or tissue antigens released at or after the time of surgery.