The free-energy profile for N2O in a hydrated 1,2-dimyristoylphosphatidylcholine (DMPC) phospholipid bilayer is calculated. The N2O molecule is preferentially concentrated in the tail region of the DMPC lipid and there is no free-energy barrier for the diffusion of N2O from an aqueous environment into the lipid. Although the dipole moment of N2O is rather small, our calculation indicates that the N2O partition coefficient is strongly influenced by electrostatic interactions. On the other hand, the van der Waals interaction overwhelms the steric effect and causes N2O concentration to be greatest at a location close to the beta-carbon of the 1-myristoyl group. (C) 2010 Elsevier B.V. All rights reserved.