To evaluate granulocytapheresis (GCAP) in active ulcerative colitis (UC), with particular attention to the long-term effects of such treatment. We included 80 patients with UC. Activity of the disease was evaluated by clinical activity index and endoscopic index. Patients were randomly divided in two groups: Group A received a five-session (1 session/week) treatment with GCAP, Group B were treated with i.v. or i.m. methylprednisolone (MP). Concomitant therapy with oral 5-aminosalicylic acid (5-ASA) 2.4 g/day was maintained in both groups. Subjects who achieved a remission were clinically and endoscopically followed for 12 months after the end of GCAP or MP. Remission was observed in 72.5% of those treated with GCAP versus 50% of those treated with MP. After a 12-month follow up, a sustained remission was recorded in 40% of those treated with GCAP and in 25% of those treated with MP. During the GCAP only a transient mild headache was recorded in 10% of patients, whereas side-effects were observed in 50% of those treated with MP (P < 0.05). GCAP results were superior to MP for the treatment of UC, even though no statistically significant difference was observed. Side-effects in the GCAP group were significantly lower than in the MP group. This new therapeutic approach seems able to maintain the condition of remission for a longer time after a flare. In fact, the patients who had obtained a remission after a course of CGAP showed fewer relapses during the follow up compared to the patients treated with MP.