The conformation of the polypeptide melittin in lipid membranes as detd. by Raman spectroscopy is a bent a-helix formed by the mainly hydrophobic residues 1-21, and a nonhelical C-terminal segment of the hydrophilic residues 22-26. Fluorescence quenching expts. on tryptophan (Trp)-19 reveal that all C-termini are located on that side of a vesicular membrane to which melittin was added. By fluorescence energy transfer between unmodified and modified Trp-19 residues, melittin is shown to aggregate in membranes predominantly in the form of tetramers. These and previous results on the location and orientation of melittin permit the development of a model for the structure of melittin tetramers in membranes. The hydrophilic sides of 4 bilayer-spanning helixes face each other to form a hydrophilic pore through the membrane. [on SciFinder (R)]