Antibodies to ribonucleoproteins (RNP) and to the Sm antigen in sera from patients with mixed connective tissue disease (MCTD) and systemic lupus erythematosus were studied using the techniques of immunoblotting and immunoprecipitation of U small nuclear RNPs. A cross-sectional study indicated that antibodies reacting with a 68K protein were associated with anti-RNP specificity in MCTD, but rarely occurred in systemic lupus erythematosus patients' sera. A longitudinal study demonstrated the persistence of MCTD blotting patterns over many years, and the subsequent disappearance of those specificities in sera from patients who were in prolonged remission.