This report describes the case of a patient with a 14-month course of severe oligoarthritis associated with acne. Pure cultures of Propionibacterium acnes were isolated from synovial tissue and synovial fluid specimens collected from the same joint after a 4-month interval. After 2 months of treatment with roxithromycin 300 mg/day, rifampicin 1,200 mg/day, and a nonsteroidal antiinflammatory drug (NSAID), followed by 4 months of treatment with azithromycin 1 gm/week and an NSAID, the synovitis persisted. Cultures of skin lesions and synovial fluid at this time were negative. Although P acnes has previously been isolated from bone specimens obtained from patients with osteitis associated with acne, this is the first report of the isolation of this microorganism from the synovial tissue of a patient with arthritis associated with acne. Our findings raise the question of the role of P acnes in the pathogenesis of arthritis associated with acne.