Falsely low levels of factor XII (FXII) have been documented in patients who are lupus anticoagulant positive (LA+). In addition, we have previously noted a surprisingly high incidence (20.9%) of apparently true FXII deficiency in patients who were LA+. We have hypothesised that this may be partly due to the presence of antibodies to FXII. The aim of the present study was to investigate whether LA+ patient plasmas contain antibodies directed either against FXII or FXII in association with phospholipids. Plasma samples from 60 blood donors, all LA negative, and 51 LA+ patients were tested using ELISA assays employing purified FXII, phosphatidylserine (PS) and phosphatidylethanolamine (PE). We have identified seven patients whose plasma contained either IgG or IgM that reacted with purified FXII in the absence of PS or PE. When PS was included in the assay system four additional patient plasmas were shown to contain either IgG or IgM that reacted with FXII. The plasma of one patient contained IgG that reacted with FXII both in the presence and absence of PS. There was no reactivity to FXII with either IgG or IgM when PE was included in the assay system. Affinity purified IgG from three patients whose plasma reacted with FXII in the ELISA assay in the absence of PS, gave a positive reaction in an immunoblot assay. These results suggest that FXII antibodies are present in a significant proportion of LA+ patients and may lead to an erroneous diagnosis of FXII deficiency.