This is a randomized, double-blind placebo-controlled pharmacologic intervention trial in HNPCC patients and carriers (with or without prior clinical manifestations). The study arms are: 1) cyclooxygenase-2 (COX-2) inhibitor or NSAID at dose #1 p.o. BID, 2) cyclooxygenase-2 (COX-2) inhibitor or NSAID at dose #2 p.o. BID, and 3) placebo. There will be 18 patients randomized to each of the arms. The study drugs will be given for twelve months (365+/- 10 days). Assessment of endoscopic, histopathologic, and cellular endpoints will be conducted at baseline, three, and twelve months on study drug or placebo. Safety monitoring will occur via in- patient interviews with exams at months three and twelve; blood and UA's at months one, three, six, nine, and twelve; and via telephone interviews at monthly (at weeks two and four of month one) intervals. A post- administration telephone call to evaluate side effect resolution will occur at month 14, in those with side effects at termination. A parallel project involving approximately 20 subjects will be conducted at another NCI-designated site; NCI will coordinate the efforts and activities of both sites.