The solution conformations of seven dodecasubstituted porphyrins, which generally show extremely nonplanar structures in the crystalline state, have been investigated using a method that combines proton NMR spectroscopy and molecular mechanics calculations. By comparison of the proton paramagnetic shifts measured for cobalt(II) complexes of these porphyrins with the dipolar shifts calculated using geometric factors obtained either from crystallographic data or from molecular mechanics structures, it is determined that the conformations of the macrocycles and their substituents are similar in solution and in the crystalline state. Thus, the nonplanar cobalt(II) porphyrins that have well-defined cavity structures in the crystalline state retain these cavities in solution. Variable-temperature proton NMR spectroscopy is used to estimate the dynamic stabilities of the cavity structures. The porphyrins with cavities are found to behave differently from planar porphyrins without cavities with regard to the formation of pi-complexes with 1,3,5-trinitrobenzene. It is suggested that the cavities may modulate a range of porphyrin-substrate interactions, potentially making these porphyrins useful as regio- and stereoselective oxidation catalysts and in the preparation of complexes with well-defined ligand orientations.