Background: Many patients with ulcerative colitis (UC) respond to mesalamine therapy within 8 weeks. Those not achieving remission after 8 weeks are often treated with steroids or other immunosuppressive therapies. This study aimed to determine the effect of 8 weeks' high-dose MMX mesalamine extension therapy in patients with active, mild-to-moderate UC who had previously failed to achieve complete remission in 2 phase III, double-blind, placebo-controlled studies of MMX mesalamine (SPD476-301 and -302).Methods: Patients with active, mild-to-moderate UC who did not achieve clinical and endoscopic remission after <= 8 weeks' treatment with MMX mesalamine (2.4 or 4.8 g/day), ASACOL (R) (mesalamine) delayed-release tablets 2.4 g/day, or placebo in the phase III Studies received MMX mesalamine 4.8 g/day for 8 weeks. The aim was to assess remission at week 8. defined as a total modified UC Disease Activity Index score of <= 1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment score and sigmoidoscopy score of <= 1, no mucosal friability and a >= 1 point reduction from baseline in sigmoidoscopy score. Results: Overall, 304 patients who entered this acute extension were evaluated; 59.5% achieved remission at week 8. Remission rates were similar irrespective of prior treatment in the initial acute phase III Studies. Conclusions: Most patients with mild-to-moderate UC who fail to achieve remission with up to 8 weeks' initial mesalamine therapy can achieve clinical and endoscopic remission following a further 8 weeks' treatment with high-dose MMX mesalamine therapy, thereby avoiding step-up therapy.