Lipid-induced secondary structures and orientations of the two enantiomeric [Leu5]-enkephalins, L-Tyr-Gly-Gly-L-Phe-L-Leu, and D-Tyr-Gly-Gly-D-Phe-D-Leu, on flat multi-bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were examined with polarized attenuated total reflection IR (IRATR) spectroscopy and molecular mechanics procedures. The membrane-bound peptides showed identical IR spectra in the amide I and II band regions that indicated membrane-induced secondary structures and specific orientations of the non-zwitterionic molecules. A Lorentzian band shape analysis based on second derivatives of the original curves and observed band polarizations suggested the presence of helical structures (beta III- and alpha-turns), oriented more or less perpendicular to the membrane surface. Other folded structures, e.g. beta I- and gamma turns, were not excluded. Molecular modelling of non-zwitterionic (Leu5)-enkephalin with two beta III-turns or an alpha-turn resulted in essentially four low-energy conformers containing (i) two beta III-turns, (ii) one alpha-turn, (iii) a beta III-turn fused to an alpha-turn, and (iv) a beta III-turn fused to a beta I-turn as in the crystallographic molecular conformation described by Aubry et al. [Biopolymers 28, 27-40 (1989)]. Zwitterionic [Leu5]-enkephalin with two beta III-turns collapsed to a C13 turn (a distorted alpha-turn) bridged by a gamma I-turn (v). The alignment of the amide I oscillators within the helical structures, (i), (ii) and (iii), and the double-bend structures, (iv) and (v), explained the observed amide I and II polarizations. Differences between these and other lipid-induced [Leu5]-enkephalin conformers reported in the literature may be caused by the lipid polymorphism of the model membranes used. Possible implications of the new conformers for the molecular mechanism of opioid receptor selection are discussed in terms of the membrane compartments theory.