A randomized double-blind multicentre clinical trial was carried out to verify the effectiveness and tolerance of S-adenosylmethionine (SAMe) versus ibuprofen in 150 patients with hip and/or knee osteoarthritis. Both drugs were given orally 400 mg thrice daily for 30 days. SAMe exhibited a slightly more marked activity than the reference drug in the management of the various painful manifestations of the joint disease. Minor side-effects developed in five patients of SAMe group, and in 16 patients of ibuprofen group. No drop-outs occurred. No changes were observed in the routine laboratory tests.