A central event in the development of the allergic response is the interaction between immunoglobulin E (IgE) and its cellular high-affinity receptor Fc epsilon RI. Allergen-bound IgE mediates the allergic response by binding through its Fc region to its cellular receptor on mast cells and basophils, causing the release of chemical mediators. One strategy for the treatment of allergic disorders is the use of therapeutic compounds which would inhibit the interaction between IgE and Fc epsilon RI. Using a structure-based design approach, conformationally constrained synthetic peptides were designed to mimic a biologically active beta-hairpin region of the alpha-chain of Fc epsilon RI. Two peptide mimics of the Fc epsilon RI alpha-chain were previously shown to inhibit IgE-Fc epsilon RI interactions, one a peptide comprised of L-amino acids, covalently cyclized by N- and C-terminal cysteine residues, and the other its retroenantiomer. In this paper the solution structures of these compounds are derived using NMR spectroscopy. The topochemical relationship between the retroenantiomeric compounds and the structural basis of their biological activity is described.