The long-term (mean of 16.4 +/- 4.2 months) efficacy and safety of rofecoxib (a specific COX-2 inhibitor) in maintaining the colon free of polyps in familial polyposis patients was assessed. Eight patients were treated with rofecoxib 25 mg every day. Sigmoidoscopy/colonoscopy was performed at study entry and every six months. At each endoscopy the number, size, and histological grade of all polyps were assessed, and the polyps were removed. The drug was well tolerated with no significant adverse events throughout the study. A highly significant reduction in the rate of polyp formation (70-100%) was observed in all patients from a mean number of 15.1 +/- 11.7 at baseline to 6.0 +/- 5.8 at one year and 1.6 +/- 1.6 at the end of follow-up (P = 0.016 and 0.008, respectively). No patient developed cancer or high-grade adenoma. In conclusion, Long-term use of rofecoxib is well tolerated and effective in inhibiting polyp formation in polyposis patients.