Utilizing a newly developed solid phase enzyme immunoassay for the detection of anti-phospholipid antibodies, we found that 41.7% of sera from patients with active systemic lupus erythematosus (SLE) had the anti-cardiolipin antibody and 22.7% of sera were positive for the anti-phosphatidylinositol (PI) antibody. But antibodies to lecithin, cephalin and sphingomyelin were rarely found in this assay. We also examined antibodies to the VDRL (Venereal Disease Research Laboratory) antigen which consists of cardiolipin-cholesterol-lecithin mixtures. The incidence of the anti-VDRL antibody in the IgG class was 29.2% and 25% in the IgM class, and the magnitude of these antibodies correlated well with the incidence of biological false positive serological test for syphilis (BFP-STS), but no association between the anti-VDRL antibody titre and the anti-cardiolipin antibody titre was observed. Furthermore, the cardiolipin binding activity of sera from patients with SLE was inhibited by DNA and poly(I), both of which have polynucleotide backbones structurally similar to the phosphodiester groups of cardiolipin. On the contrary, these polynucleotides failed to inhibit the PI and the VDRL binding of SLE sera. These observations may support the concept that the anti-cardiolipin antibody in sera from patients with SLE might be a part of the anti-DNA antibodies, which are serologically polymorphic in that they can react with a variety of polynucleotides, but differ from the BFP reactors.