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Publisher Summary This chapter considers the special features of the sprue group with particular reference to the part played by wheat gluten in pathogenesis. The chapter focusses on primary diagnosis of the malabsorption syndrome and the differential diagnosis of the sprue group. The primary diagnosis of the malabsorption syndrome rests upon estimation of the daily fecal fat output. Whereas the definitive diagnosis involves the estimation of presence or absence of pancreatic enzymes, study of rate of absorption of index substances, radiography, and small intestinal biopsy. Studies suggested that mucosal damage is present and that this results in defective barrier action (F22) and thus, various components of gluten pass through into the body and bring about several effects. The features having different etiological significance in various conditions that make up the sprue group are electrolyte imbalance, wheat gluten intolerance, folic acid and cyanocobalamin deficiency, and the effects of intestinal flora. The chapter discusses the mechanism of the effects of gluten in the malabsorption syndrome in the patients with gluten-induced enteropathy and patients with idiopathic steatorrhea and tropical sprue. Patients with gluten-induced enteropathy respond to the administration of gluten differently from other people due to inadequacy of the small intestinal mucosal barrier.