We describe the clinicopathological features of six patients, two with rheumatoid arthritis and four with osteoarthritis, in whom intake of sustained-release diclofenac for one or more years was associated with ulceration and or stricture of the ascending colon. All were referred for further evaluation of anemia and changes in bowel habits. Three had chronic watery diarrhea, one suffered from progressive constipation and subsequently needed a right hemicolectomy because of complete intestinal obstruction. In five patients, colonoscopy revealed single to multiple semilunar ulcers, predominantly localized on the crest of the haustra of the ascending colon. In five of six cases the lumen was narrowed, from slight accentuation of the haustrum to almost pinhole-like concentric stenosis. All except one patient had multiple diaphragm-like strictures. The macroscopic and microscopic appearances closely resembled those of similar lesions previously described in the terminal ileum in patients treated with nonsteroidal anti-inflammatory drugs. It appears that the slow-release form of a nonsteroidal anti-inflammatory drug, such as sustained-release diclofenac, predisposes to manifestations of such lesions in the ascending colon.