A comparison of clinical, immunological and HLA-D region antigen features was made between 22 patients with mixed connective tissue disease (MCTD) and 118 patients with systemic lupus erythematosus (SLE), scleroderma or primary Sjögren's syndrome. The MCTD patients had hypergammaglobulinemia more often than did those with SLE and scleroderma, but had less skin ulceration, serositis, nephritis, central nervous system disease and hypocomplementemia than the SLE patients. The frequencies of HLA-DR4 and its Dw4 subtype were significantly increased in MCTD as compared with both the other patient groups and healthy controls. Anti-RNP antibodies and the clinical characteristics together seem to illustrate a disease syndrome which is clinically and genetically distinct and fits with the prevailing concept of MCTD.