In normal adults intestinal permeation of ingested Cr-51-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of Cr-51-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and Cr-51-EDTA (50-mu-Ci) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/1) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of Cr-51-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (> 1.06%). In contrast, although seven colitics had a Urinary excretion of Cr-51-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and Cr-51-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.