Independent experimental and theoretical studies of the unfolding of barley chymotrypsin inhibitor 2 (CI2) are compared in an attempt to derive plausible three-dimensional structural models of the transition state. A very simple structure index is calculated along the sequence for the molecular dynamics-generated transition state models to facilitate comparison with the Φ(F) values. The two are in good agreement overall (correlation coefficient = 0.87), which suggests that the theoretical models should provide a structural framework for interpretation of the Φ(F) values. Both experiment and simulation indicate that the transition state is a distorted form of the native state in which the α-helix is weakened but partially intact and the β-sheet is quite disrupted. As inferred from the (I)F values and observed directly in the simulations, the unfolding of CI2 is cooperative and there is a 'folding core' comprising a patch on the α-helix and a portion of the β-sheet, nucleated by interactions between Ala16, Ile49 and other neighbouring residues. The protein becomes less structured radiating away from this core. Overall the data indicate that CI2 folds by a nucleation-collapse mechanism. In the absence of experimental information, we have little confidence that the molecular dynamics simulations are correct, especially when only one or a few simulations are performed. On the other hand, even though the experimentally derived Φ values may reflect the extent of overall structure formation, they do not provide an actual atomic-resolution three-dimensional structure of the transition state. By combining the two approaches, however, we have a framework for interpreting Φ(F) values and can hopefully arrive at a more trustworthy model of the transition state. The process is in some ways similar to the combination of molecular dynamics and NMR data to solve the tertiary structure of proteins.