Endoscopy is increasingly being used to obtain duodenal biopsy specimens in suspected small intestinal malabsorption. We have prospectively evaluated the effect of standard and jumbo biopsy forceps, as well as the mode of orientation of the specimens (naked eye or stereomicroscopy), on duodenal biopsy weight, length, depth, and orientation in 18 consecutive patients. A pair of biopsy specimens was obtained from each patient by each type of forceps in random order. After they had been weighed, one biopsy specimen from each pair was oriented stereomicroscopically and all four were blindly evaluated by two pathologists. The biopsy specimens obtained with the jumbo forceps were significantly larger (15.9 +/- 6.9 mg, mean +/- SD) and longer (0.6 +/- 0.2 cm) than those obtained with the standard forceps (8.0 +/- 1.3 mg, 0.4 +/- 0.2 cm, respectively; p < 0.001). Seventy-two percent of the jumbo biopsy specimens that were oriented with stereomicroscopy included a minimum of four villi in a row, as compared to 44% of the eye-oriented jumbo specimens and less than 39% of the standard specimens, irrespective of the mode of orientation (p = 0.02). These results indicate that the jumbo forceps is superior to the standard, because it produces a larger duodenal mucosal specimen, usually suitable for optimal histologic evaluation when oriented with stereomicroscopy.