Fourteen patients with polyarthritis, Raynaud's phenomenon/sclerodactyly, and circulating (U1)RNP antibodies were followed up for 10 years. All patients could be classified as having the mixed connective tissue disease at the end of the follow-up. The immunoblotting analysis revealed marked heterogeneity in the ribonucleoprotein antibody profiles. The antibodies were mainly of the IgG isotype but in four sera only IgA and/or IgM type antibodies were demonstrated. Three patients who were found to have anti-RNP by the immunodiffusion assay proved negative for anti-U-RNP antibodies by immunoblotting. Patients with antibodies against the BB' polypeptides of U-RNP particles had a disease characterized by non-erosive arthritis, sclerodactyly and cutaneous manifestations. Patients who had antibodies against the 70 kD polypeptide of U1-RNP particles only had an erosive polyarthritis. However, these patients did not tolerate treatment with either gold salts or with D-penicillamine. Thus, the classification of the RNP antibodies by immunoblotting technique seemed to define patient groups whose disease took differing courses.