The efficacy and safety of the new non-steroidal antiinflammatory drug flunoxaprofen were compared with those of naproxen in a cross over clinical study in patients with classical or definite rheumatoid arthritis (RA). Twenty female out-patients in the active phase of the disease were randomly assigned to one of the two groups studied; one group (A: 10 patients, mean age 51 years) received flunoxaprofen 400 mg/day p.o. for 30 days, followed by a 7-day wash-out period before starting the second treatment, with naproxen 500 mg/day p.o. for 30 days. Another group (B: 10 patients, mean age 58 years) received naproxen before flunoxaprofen and followed the same schedule of group A. The results showed that flunoxaprofen and naproxen have essentially equivalent therapeutical effects in controlling painful and functional symptoms of RA: both treatments resulted in a significant relief of spontaneous diurnal and nocturnal pain, pain on active and passive motion, morning stiffness, and in a significant improvement of grip strength and Richtie's index. None of the two drugs modified biochemical parameters of inflammation (ESR, CPR) or the laboratory variables measured to assess the tolerability of flunoxaprofen (hepatorenal function tests; haematological parameters). Flunoxaprofen was found to be very well tolerated: this feature together with the good therapeutic efficacy makes flunoxaprofen a very safe and useful tool in the management of severe chronic disease such as RA.