The family of antiphospholipid antibodies (aPL) includes a heterogeneous population of autoantibodies whose specificity is directed against not only phospholipids, but their complex with plasma proteins. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed to screen the aPL family which is associated with thrombotic complications in patients with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The clinical significance of other aPL tests, including antibodies against phosphatidylserine (aPS), phosphatidylinositol (aPI), phosphatidic acid (aPA), phosphatidylcholine (aPC) and phosphatidylethanolamine (aPE), has not been established. The purpose of this study was to evaluate whether multiple aPL tests have enhanced diagnostic value for APS. We tested IgG/M/A aPS, aPI, aPA, aPC and aPE by ELISA using 10% bovine serum as blocking and sample diluent in 26 SLE patients with clinical manifestations of APS, but negative for both aCL and LA (Group 1). The results were compared with 32 SLE patients without any features of APS (Group 2) and 24 SLE patients with APS (aCL and/or LA positive) (Group 3). In Group 1, 1/26 (4%) was positive for IgA aPE, less frequent than in other groups, and none of the patients had any other aPL. In Group 2, 1/32 (3%) was positive for aPS, two (6%) for aPI, one (3%) for aPA and four (12.5%) for aPE. None was positive for aPC. In the third group, 13/24 (54%) were positive for aPS, 11 (46%) for aPI, 15 (63%) for aPA, four (17%) for aPC and seven (29%) for aPE. Since aPE was found in some patients, we extended the study, including 207 SLE patients, and tested aPE. IgG/M/A aPE was found in six (3%), 10(5%) and 21 (10%), respectively, but no association was found between aPE and any clinical features of APS. This study suggests that screening by multiple aPL tests does not increase the diagnostic yield in APS.