Amylase inhibition has gastrointestinal and metabolic effects that may aid in the treatment of diabetes and obesity. We tested whether 4 g of a commercially available wheat amylase inhibitor (WAI) affected postprandial carbohydrate (CHO) absorption and plasma glucose or hormones. Twelve persons (four lean and four obese nondiabetics and four obese type II diabetics) were studied on 2 separate days. After eating a weight maintenance diet (55% CHO, 20% protein, and 25% fat, as percentage of calories) for 3 days, subjects ate a breakfast containing 650 kcal, the same proportion of nutrients as calories, and in random order, either WAI or no WAI. Breath H2 and plasma glucose and hormones were measured every 15 and 30 min, respectively, for 7 h. WAI decreased the delta peak postprandial plasma glucose concentrations in 10 of 12 subjects (p < 0.05) and increased the breath H2 levels in 11 (p = 0.02); the increases in breath H2 were small, generally <20 ppm. No subject experienced a change in stools, diarrhea, or bloating. In response to WAI, gastric inhibitory peptide decreased (p < 0.05), peptide YY increased (p < 0.05), and there was a trend toward increased human pancreatic polypeptide (p = 0.07). Although WAI delays CHO absorption and reduces peak postprandial plasma glucose concentrations, overall CHO malabsorption is minimal (as reflected by breath hydrogen and hormones) and without symptoms. It, therefore, may be useful in treating type II diabetes mellitus.