This study examined intestinal permeability in gastrointestinal disorders by measuring urinary recovery following oral administration of [99mTc]DTPA in 117 subjects. The mean percent of the ingested dose excreted in a 24-hr urine sample was 2.8 +/- 1.6% in 11 healthy controls, 10.8 +/- 10.2% (P less than 0.001) in 21 ulcerative colitis patients, 8.0 +/- 4.7% (P less than 0.001) in 35 Crohn's disease patients, 5.1 +/- 2.9% (P less than 0.01) in 17 patients with heterogeneous digestive disease diagnoses, and 3.2 +/- 4.7% (P greater than 0.05) in 33 patients with hepatobiliary diagnoses. Among ambulatory patients, Crohn's disease subjects, but not ulcerative colitis patients, had greater urinary recovery than the controls (P less than 0.05). The Crohn's disease activity index correlated positively with the radionuclide recovery in Crohn's subjects (r = 0.455, P less than 0.02). In a heterogeneous sample of subjects simultaneous ingestion of [99mTc]DTPA and [51Cr]EDTA produced urinary levels that were correlated positively (r = 0.556, P less than 0.001). Increased absorption of [99mTc]DTPA relative to [51Cr]EDTA, however, was noted in ulcerative colitis patients (P less than 0.05). In conclusion, increased intestinal permeability has been demonstrated by utilizing [99mTc]DTPA in Crohn's disease and ulcerative colitis patients. Although this observation appears to be a nonspecific indicator of injury, the test provides a simple objective means of establishing disease activity, which possibly may be utilized for therapeutic and investigative studies.