Primary fibromyalgia syndrome (PFS) is a non-articular rheumatic condition characterized by chronic muscular pain. We have performed screening for autoantibodies in 20 women with PFS and in 19 age-matched healthy women. Fifty-five percent of the PFS patients had anti-smooth muscle antibodies and 40% had anti-striated muscle antibodies. None of the control subjects had any muscle antibodies. There was no significant difference in frequency of the remaining autoantibodies between the groups investigated. The present study indicates autoimmune responses in PFS against antigens of the diseased tissue itself, a finding which may be secondary to the disease or have relevance to the still obscure pathogenesis of the syndrome.