Small peptide catalysts containing modified histidine residues are reported that effect enantioselective acylation reactions. The catalysts described include octapeptide beta-hairpins (e.g., 11) that exhibit high selectivities (up to k(rel) = 51), tetrapeptide beta-turns (e.g., 7) that afford moderate selectivities (up to k(rel) = 28), and several simple derivatives of the modified histidine amino acid that do not exhibit appreciable enantioselectivity. Supporting structural studies (H-1 NMR and X-ray) are presented which lead to the proposal of a model in which catalyst rigidity and structural complexity contribute to higher degrees of enantioselection. A covalently rigidified octapeptide (20) is prepared through solid-phase Ru-catalyzed ring-closing metathesis; kinetic evaluation of this peptide reveals that substituents along the peptide backbone may be more important than covalent stabilization of a structural motif. Detailed kinetics studies on the most selective peptide catalysts are presented that suggest the reactions are first order in catalyst and substrate. Additional kinetic studies indicate unambiguously that enantioselectivities are due to specific acceleration of reaction for one substrate enantiomer, rather than the deceleration of the reaction for the other. The results are presented in the context of a possible enantiomer-specific hydrogen-bonding interaction in the stereochemistry-determining step for these processes.