Elafin, a specific inhibitor of elastase, is thought to play a regulatory role in inflammation. An NMR-derived solution structure of recombinant elafin has been reported [Francart et al. (1997) J Mol Biol 268:666], although the conformation of its flexible N-terminal part is not established. There is experimental evidence that the N terminus (residues 1-15) of elafin interacts with the cell membrane. To explore the conformational preferences of residues in this region, we have performed Monte Carlo simulations of the peptide in water, in cyclohexane, and in a model membrane. Additionally, 3.7-ns molecular dynamics with explicit water was carried out. The main results were that the hydrophobic environment stabilizes an a helix in the region 6-11, the peptide is unordered in water, and it is attached to the membrane via the amphiphilic α-helix 6-11, which inserts with its N terminus forming an angle of about 60° to the membrane plane. We therefore assume that in nonpolar media the N-terminal part of elafin forms a short α helix which might act as a membrane anchor.