Lipid bilayers supported by nanoporous xerogel materials are being explored as models for cell membranes. In order to better understand and characterize the nature of the surface–bilayer interactions, several oxide and organic nanoporous xerogel films (alumina, titania, iron oxide, phloroglucinol–formaldehyde, resorcinol–formaldehyde and cellulose acetate) have been investigated as a scaffold for vesicle-fused 1,2-dioleoyl- glycero-3-phosphocholine (DOPC) lipid bilayer formation and mobility. The surface topography of the different substrates was analyzed using contact and tapping-mode atomic force microscopy and the surface energy of the substrates was determined using contact angle goniometry. Lipid bilayer formation has been observed with fluorescence microscopy and lateral lipid diffusion coefficients have been determined using fluorescence recovery after photobleaching. Titania xerogel films were found to be a robust and convenient support for formation of a two-phase DOPC/1,2-distearoyl- glycero-3-phosphocholine bilayer and domains were observed with this system. It was found that the cellulose acetate xerogel film support produced the slowest lipid lateral diffusion.