The conformation of melittin, a surface-active polypeptide, in solution was studied by CD spectra between 190 and 240 nm. The molecule was essentially unordered (possibly with a trace of helix) in water without salt at neutral pH. Upon deprotonation of four of the six cationic groups a t pH 12 the polypeptide became partially helical (about 35%). The addition of NaDodSO, to an aqueous melittin solution first caused the solution to become turbid but it became clear again in excess surfactant solution. The conformational changes depended on the molar NaDodS0,imelittin ratio, R. With R from 2.34 to 23.4, the melittin solution was turbid and the polypeptide conformation was probably a mixture of a-helix and p-sheets. This was supported by the ir spectrum of the turbid solution, which indicated the presence of both conformations. With R = 46.8 or 468 11 or 10 mM NaDodSO,) the polypeptide conformation was characteristic of an a-helix, about 70-80% of the molecule, regardless of whether the surfactant was above or below its critical micelle concentration. This compared well with the x-ray results of 92% helix in crystals. The lower helicity of melittin in NaDodSO, solution might be attributed to the end effects that destabilize the first and last turn of an helix at its Nand C-terminus, respectively.