In membranes, phosphatidylethanolamine (PE) is usually in a lamellar phase, but it can also adopt a hexagonal II phase (HexII PE), which has been demonstrated to be immunogenic in mice and has recently been used in a new clotting assay to detect lupus anticoagulant (LA). A population of 58 patients susceptible of having LA or antiphospholipid antibodies (aPLA), was screened for reactivity to HexII PE using the new clotting assay and for the presence of anti-PE antibodies (aPEA) using ELISA. The patients could be classified as follows: 26 systemic lupus erythematosus, 14 primary antiphospholipid syndromes and 18 miscellaneous non autoimmune disorders. HexII PE reactivity was detected in 22 patients. It was significantly more often associated with LA-positivity (20/29) than with LA-negativity (2/29), (p < 0.0001). However, 9 patients with LA had negative HexII PE assays. Anti-PE antibodies were detected by ELISA in only 12% of the cases. No correlation was observed between the distribution of aPEA and that of HexII PE reactivity. Interestingly, 2 LA- and aPLA-negative patients exhibited HexII PE reactivity. The absence of identity between the distribution of HexII PE reactivity and that of either LA or aPEA indicates that this new assay has its own specificity. It might detect antibodies to the immunogenic hexagonal PE and may therefore have a broader scope than that proposed initially. Although in the studied populations, no significant relationship could be found between HexII PE positivity and clinical complications (thrombosis and/or recurrent fetal losses), it might be associated with other complications of the antiphospholipid syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)