In severe trauma, sepsis or during surgery, bacterial lipopolysaccharide (LPS) frequently enters the circulation. Persons with high levels of high-density lipo-protein (HDL) have previously demonstrated higher monocyte procoagulant activity (PCA) when whole blood is challenged with LPS. The aim of the study was to investigate the distribution of radiolabelled LPS (¹²⁵I-LPS) in plasma from six persons with high (2.14–2.82 mmol 1⁻¹) and six persons with low (0.54–1.04 mmol 1⁻¹) HDL, subjecting plasma to fast protein liquid chromatography (FPLC), or agarose electrophoresis followed by quantitative autoradiography. In heparin plasma ¹²⁵I-LPS was located mainly in parts of plasma containing low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) and the immunoglobulins, and located to a lesser extent in HDL. However, persons with high HDL showed significantly higher binding of ¹²⁵I-LPS to HDL and the immunoglobulins, probably to IgG, and significantly lower binding to LDL/VLDL. In calcium-depleted plasma (EDTA) ¹²⁵I-LPS demonstrated a sharp increase in the binding to HDL, combined with a persistently high binding to LDL/VLDL and binding to the immunoglobulins was almost eliminated in all subjects investigated. Likewise, the binding of ¹²⁵I-LPS to HDL in EDTA plasma was also significantly higher and to LDL/VLDL significantly lower in persons with high HDL. This study demonstrates that the distribution of ¹²⁵I-LPS in heparin and EDTA plasma from persons with high or low HDL is different, which is presumed to be of importance concerning the various bioactivities of LPS.