We describe autoantibodies reactive with the signal-recognition particle (SRP) in serum of a patient with polymyositis. The serum specifically immunoprecipitated the SRP from human erythroleukemia (K562) cell extracts. Analysis of immunoblots revealed that the serum contained autoantibodies specific for the 54-kDa protein of the SRP but had little or no reactivity with its other five proteins. Indirect immunofluorescence of human laryngeal carcinoma (HEp-2) cells confirmed that the ribonucleoprotein immunoprecipitated by this serum is found mainly in the cytoplasm. This autoimmune serum may be useful for studying the function of the 54-kDa subunit of the SRP in binding to signal sequences or in interacting with other components of the translational machinery.