A series of beta-hairpin peptides based on variations of the TrpZip2 sequence, SWTWENGKWTWK, of Cochran and co-workers were studied using electronic circular dichroism (CD) and infrared (IR) spectra by varying temperature and pH. Selected tryptophan residues were substituted with Val to test the impact of specific Trp interactions on hairpin stability. Native-state structures of two of the variants were determined using 2-D NMR and shown to have the same cross-strand edge-to-face Trp-Trp interaction as in Trpzip2. Thermally induced conformational changes of the hairpins formed with these various sequences were studied with CD and IR. Thermodynamic analyses of the temperature variation of both IR (as analyzed using the amide I' frequency shift) and CD (intensity) spectra were fit to a two-state model that yielded different T(m) values, consistent with a multistate process of folding/unfolding. At low pH these differences were minimized, suggesting a change in the energetics. Cross-strand interacting Trp residues with an edge-to-face orientation had the strongest impact on hairpin stability, as judged by CD and IR data. The diagonal interaction between Trp2 and Trp9, which have a more parallel orientation in Trpzip2, contribute to the spectral response but do not independently stabilize the structure. Comparative study of these various physical interactions emphasizes the complex folding pathways that are important even for these small peptides.