Isolated subunits from the crystalline cell surface layer (S-layer) of Bacillus coagulans E38-66 were recrystallized on positively charged liposomes. The liposomes were composed of dipalmitoylphosphatidylcholine/cholesterol and stearylamine. The natural arrangement of the S-layer subunits on the bacterial surface is as an oblique (p2) lattice. The subunits attached to positively charged liposomes by their inner face (which bears a net negative charge) in an orientation identical to the lattice on intact cells. The S-layer protein, once recrystallized on liposomes, was crosslinked with glutaraldehyde and subsequently used as a matrix for the covalent attachment of macromolecules. The high stability of S-layer-coated liposomes and the possibility for immobilizing biologically active molecules on the crystalline array may offer potential in various different liposome applications.