Twenty-five antinuclear antibody (ANA) negative patients with systemic lupus erythematosus (SLE) or lupus-like disease were compared to 91 ANA positive patients with SLE for clinical and biological symptoms. Cutaneous symptoms were infrequent in ANA negative patients (p less than 0.03). Thrombocytopenia (p less than 0.001), venous or arterial thrombosis (p less than 0.02) as well as cerebral infarction (p less than 0.001) were more frequent. Three types of antiphospholipid antibodies were determined by different methods; the VDRL, the lupus anticoagulant and an ELISA for IgG anticardiolipin antibody (aCL). The frequency of a positive VDRL test was significantly higher in the ANA negative group (p less than 0.05). Correlation studies suggest that the 3 methods are not redundant and detect overlapping but not identical antibodies. Of the 3 antiphospholipid antibody assays, only the IgG aCL test was significantly associated with thrombosis in the ANA negative group (p less than 0.02).