Mixed connective-tissue disease (MCTD) is an autoimmune disorder with coexistence and overlap of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); and, occasionally, Sjögren’s syndrome. The presence of antibodies to specific components of U1-ribonucleoprotein (U1-RNP) complex is the immunological marker for the diagnosis of MCTD. The complex is composed of U-riched small nuclear RNA and a set of proteins, the 68 kDa (or 70 kDa) U1-specific protein plus proteins A and C and the Sm antigens (B, B`, D1, D2, D3, E, F, and G). Antibodies against the sn-RNP complex are directed against Sm as well as the 70 kDa U1-specific proteins plus proteins A and C. It is now known that the availability of RNP antigen in the absence of Sm is a good marker for MCTD.