Diamine oxidase (DAO) is a cytoplasmic enzyme found primarily in the villus epithelial cells of the small intestine. Serum DAO levels have been evaluated as a potential marker of intestinal disease in a variety of disorders, including gut atrophy, ischemia, and inflammation. In this study serum and tissue DAO levels were evaluated during intestinal adaptation. Twenty dogs were divided into 4 groups: sham laparotomy (n = 5), and 25% (n = 5), 50% (n = 5), and 75% (n = 5) distal enterectomy. Serum DAO activity (basal or postheparin) was measured prior to and 2 days, 4 weeks, 8 weeks, and 12 weeks after operation. Tissue DAO and changes in intestinal length, mucosal protein content, and villus height were measured at sacrifice 12 weeks later. Intestinal remnant length and protein content increased significantly with 50 and 75% resection. Tissue DAO activity was significantly decreased with any enterectomy. Serum postheparin DAO activity was significantly greater than basal at all time points but there was no significant change in either basal or postheparin DAO levels at any time following resection. It is concluded that serum DAO levels are not changed during the early adaptive period following intestinal resection and thus would not be useful as a marker of this process. Tissue DAO levels were diminished during adaptation, suggesting that tissue DAO activity is influenced not only by mucosal mass but by cellular metabolism and the proliferative status of the mucosa.