Musculoskeletal manifestations and autoimmune phenomena are recently recognized complications of infection with human immunodeficiency virus (HIV). Patients with HIV infection share several clinical and serologic features with patients with systemic lupus erythematosus and Sjögren's syndrome; these similarities may lead to diagnostic confusion. The significance of the presence of different types of autoantibodies in HIV-infected patients is still uncertain and may reflect polyclonal B cell activation. Musculoskeletal complications--particularly arthritis, arthralgia, and myalgia--are common in advanced stages of HIV infection. Clinical characteristics and serologic findings support the premise that most of the musculoskeletal complications (e.g., Reiter's syndrome, psoriatic arthritis, acquired immunodeficiency syndrome-associated arthritis and arthralgias) are reactive in nature--either a direct consequence of HIV infection or a result of various opportunistic infections. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Further studies are needed to define the full spectrum and frequency of these musculoskeletal abnormalities.