The authors undertook a cross-sectional study to investigate the clinical associations of antiribonucleoprotein (anti-RNP) antibodies in 49 patients with systemic lupus erythematosus (SLE) without other concomitant connective tissue disorders. The traditional counterimmunoelectrophoresis (CIE) and the immunoblotting (IB) technique were compared. Clinically, special attention was given to the identification of sclerodermalike features. All patients completed a detailed questionnaire, physical examination, and additional investigations including pulmonary function tests, chest roentgenogram, radionuclide transit studies of the esophagus, and nailfold capillary microscopy. Pulmonary function testing and radionuclide transit studies of the esophagus were very sensitive for the detection of (subclinical) pulmonary and esophageal involvement, respectively. Within the relatively homogeneous SLE population, a subset was recognized that was characterized clinically by the presence of sclerodermalike features such as Raynaud's phenomenon, sclerodactyly, interstitial changes on chest roentgenogram, and decreased numbers of nailfold capillary loops, and serologically by the presence of anti-RNP antibodies. IB was somewhat more sensitive than CIE for the detection of anti-RNP (anti-Sm/anti-nRNP) antibodies but did not identify other clinical associations. Thus, anti-RNP antibodies in SLE are associated with scleroderma-associated features. For clinical practice, CIE is the technique recommended for their detection.