Leukocytapheresis (LCAP) with a leukocyte removal filter was administered to 44 patients with inflammatory bowel disease (IBD), diagnosed as ulcerative colitis (UC) in 25 and Crohn's disease (CD) in 19. Clinical and blood examinations showed no side effects in any of the patients. During intensive therapy, clinical improvement was recognized in 21 of the 25 UC patients (84%), 8 of whom had an excellent response, and in 16 of the 19 CD patients (84.2%), 4 of whom had an excellent response. The clinical improvement continued throughout the maintenance therapy in 19 of the UC patients (76%) and in 12 of the CD patients (63.2%). In both the UC and the CD patients, flow cytometry study showed that those who had improved generally had high values for the percentages of HLADR+, HLADR+CD3+, HLADR+CD8+, and CD11a+CD8+ cells before the first LCAP, and that these values decreased to near the normal range after both intensive and maintenance therapy. In the patients who showed poor response, in contrast, the values had been at or near normal before the initial LCAP administration. The clinical improvement and the findings on flow cytometry suggest that LCAP exerts an immuno-modulatory effect and is an effective therapy for patients with IBD in whom conventional drug treatments have failed.