Currently there are no widely accepted criteria for the diagnosis of MCTD. In this work we attempted to define the clinical profile of a group of 68 patients with anti nRNP antibodies, detected by immunoprecipitation in 0.6% agarose. The diagnosis of each collagen vascular disease was established in every patient, who met with the strict diagnostic criteria either at clinical presentation or during the follow-up period. Twenty-eight patients had SLE, 9 had classical erosive RA, three had PSS and one had PM. The only distinctive features in the group of SLE with anti nRNP was an increased incidence of anti Sm antibodies (p less than 0.05). In the RA group there was a trend towards a high frequency of Raynaud's phenomenon and swollen hands. At clinical presentation twenty-seven patients did not fulfil enough criteria to be diagnosed of any of the well-defined collagen vascular disease. They presented an undifferentiated syndrome, characterized clinically by Raynaud's phenomenon (100%), swollen hands (88.9%) and joint symptoms (88.9%), with scarce tendency of developing severe systemic manifestations. The main laboratory abnormalities in this group were hypergammaglobulinemia, mildly increased ESR, abnormal levels of CIC, negative anti nDNA and anti Sm antibodies, and the virtual absence of hypocomplementemia. During a clinical course of 96 +/- 72.5 months only one patient evolved into another collagen disease (SLE). The clinical course in the remaining cases, was stable improving with low doses of prednisone and/or NSAID. We suggest considering this undifferentiated syndrome as a distinct entity, for which the already classical term of MCTD could be reserved.