Rofecoxib selectively inhibits cyclo-oxygenase-2 in a dose-dependent manner in humans. No significant inhibition of cyclo-oxygenase-1 is observed with rofecoxib up to doses of 1000 mg. In 4 large double-blind randomised trials performed in patients with osteoarthritis, rofecoxib 12.5 and 25 mg/day significantly improved physical functioning, assessed using the Western Ontario and McMasters Universities Osteoarthritis Index and patient or investigator global assessment, compared with placebo. In addition, rofecoxib showed similar clinical efficacy to that observed with diclofenac 50 mg 3 times daily, ibuprofen 800 mg 3 times daily and nabumetone 1500 mg once daily. Rofecoxib is also an effective analgesic in patients with primary dysmenorrhoea or postoperative dental pain and demonstrates similar analgesic efficacy to that of naproxen sodium and ibuprofen. Rofecoxib is generally well tolerated. The most common adverse events associated with rofecoxib are diarrhoea, headache, nausea and upper respiratory tract infection. There was a significantly lower incidence of upper-gastrointestinal adverse events (perforations, ulcers and bleeds) in patients with osteoarthritis receiving rofecoxib 12.5, 25 or 50 mg/day than in those receiving ibuprofen, diclofenac or nabumetone.