The interaction of apolipoprotein H (Apo H) with lipid membrane has been considered to be a basic mechanism for the biological function of the protein. Previous reports have demonstratedthat Apo H can interact only with membranes containinganionic phospholipids. Here we study the membrane-inducedconformational change of Apo H by CD spectroscopy with twodifferent model systems: anionic-phospholipid-containing liposomes[such as 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol(DMPG) and cardiolipin], and the water}methanol mixtures atmoderately low pH, which mimic the micro-physicochemicalenvironment near the membrane surface. It is found that Apo Hundergoes a remarkable conformational change on interactionwith liposomes containing anionic phospholipid. To interact withliposomes containing DMPG, there is a 6.8%increase in a-helixin the secondary structures; in liposomes containing cardiolipin,however, there is a 12.6% increase in a-helix and a 9% decreasein b-sheet. The similar conformation change in Apo H can beinduced by treatment with an appropriate mixture of water}methanol. The results indicate that the association of Apo Hwith membrane is correlated with a certain conformationalchange in the secondary structure of the protein.