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Conformational studies on the synthetic 11-aa peptide t -butoxycarbonyl (Boc)-Val-Ala-Phe-α-aminoisobutyric acid (Aib)-( R )-β 3 -homovaline (βVal)-( S )-β 3 -homophenylalanine (βPhe)-Aib-Val-Ala-Phe-Aib-methyl ester (OMe) (peptide 1; βVal and βPhe are β amino acids generated by homologation of the corresponding l -residues) establish that insertion of two consecutive β residues into a polypeptide helix can be accomplished without significant structural distortion. Crystal-structure analysis reveals a continuous helical conformation encompassing the segment of residues 2–10 of peptide 1. At the site of insertion of the ββ segment, helical hydrogen-bonded rings are expanded. A C 15 hydrogen bond for the αββ segment and two C 14 hydrogen bonds for the ααβ or βαα segments have been characterized. The following conformational angles were determined from the crystal structure for the β residues: βVal-5 (φ = –126°, θ = 76°, and ψ = –124) and βPhe-6 (φ =–88°, θ = 80°, and ψ =–118). The N terminus of the peptide is partially unfolded in crystals. The 500-MHz 1 H-NMR studies establish a continuous helix over the entire length of the peptide in CDCl 3 solution, as evidenced by diagnostic nuclear Overhauser effects. The presence of seven intramolecular hydrogen bonds is also established by using solvent dependence of NH chemical shifts.