The interaction of basic protein from human myelin with dimyristoylphosphatidylglycerol (DMPG) bilayers was investigated by Fourier transform infrared spectroscopy. The effect of protein on the lipid conformation and also the effect of lipid on the protein secondary structure were examined. The association of myelin basic protein with DMPG results in a broadening of the lipid phase transition, accompanied by an increase in the conformational order of the acyl chains at temperatures below the phase transition. While the direct contact between myelin basic protein and acidic phospholipids is believed to involve the polar region of the bilayer, infrared spectra indicate that the association between DMPG head groups and protein does not result in drastic changes in the conformation of the lipid phosphate moiety. Infrared spectra of myelin basic protein in the amide I region were analyzed quantitatively by using resolution enhancement and band fitting procedures. The above analysis suggests that in aqueous solution the protein is devoid of a-helical and @-conformations but that it contains a significant amount of turns. Upon binding to DMPG bilayers, the secondary structure of the protein is dramatically altered. The lipid-complexed basic protein adopts a highly ordered secondary structure. According to the quantitative infrared analysis, the main components of this structure are antiparallel 0-sheet (53%), a-helix (15%), and turns (15%).