Overlap syndromes (OS) are complex clinical entities in which symptoms and serological profiles of diverse connective tissue diseases, mainly systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), dermato/polymyositis and Sjögren syndrome, converge in a single patient. On the basis of the personal experience, the Authors try to classify OS from the serological point of view. Six different serological profiles have been recognized. Anti-U1RNP antibodies define the classical mixed connective tissue disease (MCTD) according to Sharp. These patients are probably most common and present with Raynaud's phenomenon and puffy hands which never reach sclerodactily. In Italian patients, the symptoms of lupus erythematosus are not as frequent as in USA patients, probably due to the prevalence of Negroes in the latter. The absence of renal involvement is, instead, common as in other series. The general trend of these patients is towards progressive systemic sclerosis and lung fibrosis. Anti-Ku antibodies define another group of patients with the same clinical symptoms as MCTD and good prognosis. Anti-Ki-SL antibodies, by contrast, characterize a less common group of patients in which the renal and the pulmonary involvement is frequent. Their prognosis is poor. Anti-Sm and anti Ro/SSA antibodies, which are more commonly found in SLE patients, may be detected also in some of the patients with OS who have a poor prognosis. Patients with anti-SSA, for example, have, as in PSS, an early onset and a rapid development of lung fibrosis. Finally, anti-La/SSB antibodies define patients who associate Sjögren syndrome to SLE or PSS.(ABSTRACT TRUNCATED AT 250 WORDS)