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B-cells are considered to play a pathogenic role in human ulcerative colitis (UC) by producing autoantibodies that cause epithelial cell damage. Here we report on a patient with intractable UC who suffered from a severe exacerbation of UC after salvage therapy with rituximab, a B-cell-depleting anti-CD20-antibody.A 58-year-old patient with active long-standing UC and unresponsiveness or adverse events to mesalamine, corticosteroids, azathioprine, methotrexate, infliximab, leukapheresis, mycophenolate mofetil, and adalimumab received 375 mg/m2 rituximab.A severe exacerbation of UC activity was noted upon therapy that required hospitalization. Subsequent studies showed a complete depletion of CD20-positive mucosal B-cells associated with a suppression of local IL-10 production.In contrast to rheumatoid arthritis patients, rituximab had deleterious effects in our UC patient by blocking IL-10 producing B-cells. Our data suggest an important anti- rather than proinflammatory role of B-cells in UC.