The diagnostic value of Tc-99m leukocyte imaging for evaluating disease activity and monitoring treatment response in ulcerative colitis was compared with that of colonoscopy. A total of 48 studies were performed in 28 patients with ulcerative colitis. Forty-six studies had both Tc-99m leukocyte imaging and colonoscopy within 2 weeks of each other, and the remaining two studies had only Tc-99m leukocyte imaging. In 46 studies, semiquantitative grading of colonic radioactivity by comparison with iliac crest marrow activity on radionuclide imaging correlated well with macroscopic grading based on Matts' criteria on colonoscopy. Fourteen (82%) of 17 studies with slight colonoscopic change showed a negative result on the radionuclide image. In 15 patients treated with glucocorticoids or leukapheresis, radionuclide imaging showed nearly the same statistical results as colonoscopy in monitoring treatment response. Tc-99m leukocyte imaging could be used as an alternative to colonoscopy to evaluate the disease activity of ulcerative colitis or to monitor the treatment response, although it is insensitive for detecting disease with only slight macroscopic changes.