Extract: Eighteen peroral intestinal biopsies were obtained from children with celiac disease. A marked impairment of the enzymatic equipment was noted in the mucosa of patients with untreated celiac disease. The surface epithelium is clearly deficient in ATP-ase, 5-nucleotidase, monoamine oxidase, leucine aminopeptidase, glucose-6-phosphatase and lactase activities. The histochemical reactions for acid phosphatase, non specific esterases, α-glucosidases and deshydrogenases are often less affected. Only alkaline phosphatase activity seems unaltered in the surface epithelium. After the start of a gluten-free diet, an improvement in the patient's clinical condition occurs within a few weeks. At the same time, there is an increase in the activity of some enzymes. The histochemical reaction for ATP-ase shows a rapid improvement. This reaction is almost normal in specimens taken 2, 3 and 5 weeks after gluten withdrawal, but it is still negative in a biopsy performed one week after the removal of gluten from the diet. In addition, the histochemical stains for several other enzymes, such as 5-nucleotidase and leucine aminopeptidase also return towards normal in a short time. Contrariwise lactase activity remains very low for several months after the beginning of the gluten-free diet. Sometimes the lactase deficiency may be responsible for clinical disturbances, i. e. ‘a secondary intolerance to lactose’. In such cases, lactose exerts some ‘toxic effect’ on the mucosa and prevents the restoration of the villi. Therefore, it is necessary to withdraw lactose as well as gluten from the diet. This intolerance to lactose is nevertheless transient and disappears after the mucosa is repaired. It should be emphasized that there is a marked discrepancy between the histologic improvement, the evolution of the enzymatic abnormalities and the clinical response after gluten withdrawal. In most cases, the biological and clinical disturbances progressively disappear in three to five weeks. The morphologic changes of the duodeno-jejunal mucosa persist much longer. Before the first two months, there is no evident improvement in the histologic appearance of the mucosa. About three months after the start of dietary treatment, the villi are noticeable again, but are still short and broad (partial villous atrophy). Complete repair may require several months and sometimes more than one year. In striking contrast, some enzymatic activities reappear very quickly. This improvement in some histochemical reactions seems to correlate closely with the rapid clinical response and, therefore, suggests that the histoenzymatic abnormalities play a prominent role in the absorptive failure of celiac disease. When the patients are put again on a normal diet, histological studies constantly show the reappearance of the mucosal lesions (subtotal villous atrophy), whereas the evolution of both clinical disturbances and histoenzymatic abnormalities is variable. Sometimes a clinical and biological relapse occurs and the histochemical reactions are again impaired. But in most cases, although severe histologic changes reappear, the clinical state and the biological tests of intestinal absorption remain satisfactory, with normal growth and no steatorrhoea. It is noteworthy to point out that, in these cases without clinical relapse, the enzymatic activities are only slightly reduced. Speculation: Although studies of more cases are needed in order to confirm these data, it appears that histochemical reactions provide a most valuable tool for the study of the mechanism involved in intestinal malabsorption. It seems likely that these reactions reflect the absorptive capacity of the small bowel mucosa. Furthermore, when some patients are put again on a normal diet, the histochemical changes could provide a practical means for predicting a relapse before the impairment of the patient's clinical condition.