Intestinal protein loss was quantified in 30 patients with Crohn's disease and its relationship to serum protein levels, the location and extent of disease, and d-xylose, B₁₂ and fat malabsorption determined statistically. Protein clearance was excessive in 21 patients, with maximal values more than 15 times normal, but serum protein levels were low in only 8 patients. Clearance values correlated well (r = 0.76) with the extent of disease as measured from radiographs, but was not related to d-xylose, B₁₂, or fat malabsorption, present in 14, 17, and 12 patients respectively. These absorption tests correlated poorly with the extent and location of disease. The results indicate that enteric protein loss is frequently excessive in Crohn's disease and, as measured by clearance studies, provides one of the best objective reflections of the extent of the intestinal lesion.