Cyclic pentapepticles are not known to exist in a-helical conformations. CD and NMR spectra show that specific 20-membered cyclic pentapepticles, Ac-(cyclo-1,5) [KxxxD]-NH2 and Ac-(cyclo-2,6)R[KxxxD]-NH2, are highly a-helical structures in water and independent of concentration, TFE, denaturants, and proteases. These are the smallest a-helical peptides in water.