Serum containing a monoclonal IgA protein from a patient with multiple myeloma gave intense immunofluorescent staining of smooth muscle fibres and the striations of skeletal muscle, cardiac muscle and thymic myoid cells. It also gave a weaker reaction with hepatocytes in a 'polygonal' pattern, and with renal glomeruli in a diffuse pattern. In culture fibroblasts, the serum stained long, parallel cytoplasmic filaments. Specificity of the staining reactions for actin was established by their prevention on serum absorption with skeletal muscle actin, but not by skeletal muscle myosin, tropomyosin or troponin, and by the demonstration that eluates obtained by acid dissociation of the serum-actin precipitates gave the same staining reactions as the original serum. Localization of the anti-actin reactivity to the monoclonal IgA protein was established by the observation that the same staining reactions were obtained with a monospecific IgA conjugate, with the eluate derived from the gamma globulin band of a serumel ectrophoretic strip, and with a purified euglobulin (IgA) fraction; also, the eluates obtained by acid dissociation of the serum actin precipitates contained monoclonal IgA.