Twenty-seven patients with CF and joint complaints were reviewed. Twelve patients had arthritis, 11 had HPO, and four had symptoms of mechanical neck and back pain. We have confirmed the association of CF with an episodic form of arthritis. For the first time, we have reported that a subgroup of these patients later develop persistent synovitis with progressive asymmetric, erosive disease. The etiology of CF arthritis is unclear, but may relate to chronic infection and immune complex mechanisms. CF arthritis can be contrasted with CF induced HPO, which is associated with worse lung disease, a male predominance, and an older mean age of onset of symptoms. Mechanical neck and back pain may relate to an associated scoliosis or kyphosis in CF.