We determined whether serological investigations can assist to distinguish between chronic idiopathic autoimmune thrombocytopenia (cAITP) and immune-mediated thrombocytopenia in patients at risk to develop systemic lupus erythematosus (SLE); 82 patients were seen in this institution for the evaluation of immune thrombocytopenia. In nine of these patients a diagnosis of SLE was made at presentation or shortly thereafter. In the remaining 73 patients with an established diagnosis of cAITP we obtained serum samples at a median disease duration of 7 years; 45 patients were investigated again 2 years later. cAITP patients suffered from their disease for up to 30 years (median 7 years, range 2-30 years) without developing clinical features of SLE. Elevated antinuclear antibodies were found in all patients with a diagnosis of SLE but also in seven patients with established cAITP. All patients who had thrombocytopenia in association with SLE had additional antibodies to anti-nDNA and/or antibodies to soluble cellular antigens. Neither in the initial, nor in the follow-up investigation, such antibodies were discernible in patients with cAITP. We conclude that patients with cAITP do not develop SLE and do not form antibodies to defined cellular antigens, even if suffering from the disease for many years. The ANA titer does not help to differentiate cAITP from thrombocytopenia of SLE. A differentiation, however, between the two diseases is possible by the combined screening for antinuclear antibodies, anti-nDNA, and antibodies to defined soluble cellular antigens.