AbstractMyosin in striated muscle exists in at least two immunologically distinct forms. Human autoantibodies specific for either form show selective muscle fiber reactivity. One group of antibodies reacts with type 2b (white) muscle fibers, the other with type 2a (red) and type 1 (intermediate) fibers. All of these antibodies react with the A band of glycerinated myofibrils. Both groups of antibodies react with cardiac muscle. Muscle‐fiber‐specific antibodies are detected in approximately 1% of sera submitted for diagnostic screening. Sera from eight patients were studied further. The two patients with antibodies against type 2b (white) muscle myosin had rheumatoid arthritis. The six patients with antibodies against type 2a (red) and type 1 (intermediate) myosin had clinical features which included various autoimmune and infectious disord