A calcitonin analogue, MCT-II, having the potential to form an amphiphilic alpha-helix from residue 8 to residue 22 with a continuous surface of aliphatic leucine side chains on the hydrophobic face of the helix has been synthesized, and its physical and biological properties have been characterized. Properties exhibited by this peptide, including self-association in the micromolar concentration range with a concomitant increase in the percentage of alpha-helical structure, formation of stable monolayers at the air-water interface, and adsorption to the surface of egg lecithin single-bilayer vesicles, demonstrate that MCT-II can readily form an amphiphilic alpha-helical structure. Though MCT-II has minimal sequence homology to any particular natural analogue from residue 8 to residue 22, it has biological activity similar to that of salmon calcitonin I for receptor binding in brain and kidney membranes, for activation of adenylate cyclase, and in hypocalcemic potency in vivo. The amphiphilic alpha-helical structure of MCT-II, therefore, is important for binding to calcitonin receptors. It is also apparent that a hydrophilic residue commonly occurring on the hydrophobic face (position 15) in the natural calcitonins is not required for high biological activity.(ABSTRACT TRUNCATED AT 250 WORDS)