Intestinal biopsy specimens from 22 patients with celiac sprue demonstrated the following: (1) Mean disaccharidase and alkaline phosphatase activities increased from low levels associated with severe mucosal lesions to higher levels with moderate or mild lesions. With mild histology, all enzymes assayed were normal, except for low lactase activity in 25%. (2) Comparison of paired specimens from adjacent sites revealed similar morphologic changes in 70% of the pairs. With respect to occurrence of normal or abnormal enzyme activity in the paired samples, lactase activity was the same in all pairs, while the other enzymes were the same in 74% to 86% of the pairs. (3) Although a clinical improvement followed fair adherence to a glutenfree diet, mild histologic changes and a complete return of enzyme activity occurred only in patients who had adhered strictly to the diet.