We report a 34-year-old man with chronic hepatitis C who showed exacerbation of ulcerative colitis during alpha-interferon (IFN alpha) therapy. Discontinuance of the IFN alpha therapy improved his symptoms, suggesting that IFN alpha administration might worsen ulcerative colitis. The administration of sulfasalazine allowed the patient to receive IFN alpha again without flare-up of ulcerative colitis. This case suggests the possible efficacy of sulfasalazine therapy in patients with ulcerative colitis complicated by some other diseases requiring IFN alpha administration.