Diphenpyramide is a non-steroidal anti-inflammatory compound which has no free ionizable or particularly reactive groups, in contrast to conventional non-steroidal anti-inflammatory agents. In animal tests, diphenpyramide showed anti-inflammatory action as powerful as that of indomethacin or phenylbutazone, with major peripheral analgesic, antipyretic and uricosuric properties. The therapeutic index was more favourable than that of the reference compounds. Diphenpyramide inhibits the synthesis of inflammatory prostaglandins and antagonizes the mediators of inflammation, but does not affect platelet aggregation or blood clotting. The major biotransformation products are biphenylacetate (BPA), which is pharmacologically active, p-hydroxy-biphenylacetate (p-HBPA) and alpha-aminopyridine (AP). The first is metabolized to p-HBPA which is excreted in the urine. The serum levels of the parent drug and BPA do not result in particularly elevated peaks. Elimination occurs mostly through the faeces. The anti-inflammatory action of diphenpyramide has been extensively proven in clinical trials in which patients with various inflammatory conditions, mainly of a musculoskeletal nature, were treated. The overall therapeutic efficacy was over 80% with a high proportion in osteoarthritis. In double-blind studies, the efficacy of diphenpyramide was significantly better than that of acetylsalicylic acid or indomethacin in osteoarthritis, and comparable with that of naproxen. The preferred dose of diphenpyramide in adults was 1000 mg/day in 2 divided doses for a period of about 30 days. The effective and safe dose in children was 13 to 33 mg/day. Side-effects were seldom reported (2.5%), were mild and transient and mainly of a gastro-intestinal nature. Specific tests on possible drug influence on the gastric mucosa showed diphenpyramide to be 'gastrosafe' both on short-term, high-dose as well as on long-term standard treatments. Biopsy and endoscopy of the mucosa failed to indicate any impairment; occult blood in stools could not be detected. Diphenpyramide seems, therefore, to be an anti-inflammatory drug that combines efficacy and tolerance in the treatment of a wide variety of inflammatory musculoskeletal disorders of primary of secondary nature, as well as the associated pain. Clinical observations also suggest that diphenpyramide could safely be administered to susceptible patients, such as children and infants or elderly, in need of effective anti-inflammatory treatment.