The ribonucleoprotein (RNP) p67 antigen was purified from rabbit thymus and used in an enzyme linked immunosorbent assay (ELISA) with low interassay variability to detect IgG antibodies to p67 in patients with autoimmune connective tissue diseases. These antibodies were found in eight (80%) patients with a clinical diagnosis of mixed connective tissue disease (MCTD) but also in 27 (40%) patients with systemic lupus erythematosus (SLE). Sixty six per cent of the 12 patients with SLE with high levels of antibodies to p67 (> 50 U) had three or more features of MCTD, including myositis, fibrosing alveolitis, Raynaud's phenomenon, and sclerodactyly. Antibodies to the p67 RNP were not associated with the presence or absence of renal disease in the patients with SLE. This study suggests that antibodies against the p67 RNP are markers for clinical features of MCTD even in the context of SLE.