Repeat proteins are constructed from linear arrays of a common structural unit. The physical characteristics that describe the resulting structure depend on the sequence composition of the repeating unit, the number of repeats, and the architectural arrangement of the units with respect to each other1.The tetratricopeptide repeat is 34 amino acids in length, and consists of a pair of anti-parallel “A” and “B” α-helices. Regan and coworkers have designed a consensus TPR (cTPR) sequence and characterized the thermodynamic stability and kinetics of folding of a series of cTPRs (1-10 repeats) with a “solubilizing” C-terminal “S” helix2.3.4. Their stability data were fit using a homopolymeric model in which the A, B, and S helices were treated as energetically equivalent, although there are significant differences in sequence and packing between the A and B helices. Because the A:B helix ratio was the same in all constructs studied, the homopolymeric model was sufficient to model the thermodynamics of unfolding, despite potential intrinsic energy differences between the different helices. Furthermore, the energy associated with each respective interfacial interaction (AiBi+1, BiAi+1,BiSi+1) was not able to be resolved.To determine whether the A and B helices differ in intrinsic stability (ΔGA and ΔGB), and whether interfacial stability (ΔGAB and ΔGBA) values are synonymous, we constructed a series of cTPRs that vary in length, and in the ratio of A to B helices. In addition, we include constructs lacking the C-terminal S-helix. Urea-induced unfolding transitions suggest cooperative folding with a moderate level of nearest-neighbor coupling, as was found by Regan and coworkers. Our results indicate that stability is heterogeneously distributed within cTPR arrays. Although the A and B helices have similar intrinsic stabilities, the energy arising from BiAi+1 interactions contribute more to stability than their AiBi+1 counterparts.