The development of unnatural oligomers that adopt predictable secondary structures has led to increased interest in expanding the conformational repertoire of foldamers to include discrete, cooperatively folded tertiary and quaternary structures. Here we report the first examples of heterogeneous quaternary structure: stable tetrameric helix bundles incorporating both alpha-peptides and alpha/beta-peptide foldamers. The results suggest that hydrophobic interactions in the core of the helix bundle contribute to the stability of the assembly, as do cyclic beta-amino acid residues within the alpha/beta-peptide. These observations demonstrate that secondary structural elements in well-folded tertiary or quaternary structures need not have the same backbone composition. Our findings highlight the prospect that diverse combinations of foldamer and alpha-peptide subunits could lead to folding and/or assembly behavior reminiscent of that necessary for complex protein function.