The effect of hydrostatic pressure upon solutions of chymotrypsinogen and lysozyme at room temperature has been followed by employing a new technique [Chryssomallis, G. S., Drickamer, H. G., & Weber, G. (1978) J. Appl. Phys. 49, 3084] that permits the measurement of fluorescence polarization at pressures of up to 10 kbar. Lysozyme shows a stable, reversible 60% increase in apparent volume when the pressure is raised to 9 kbar. This can be given a simple interpretation in terms of solvent penetration of the structure at higher pressures. In contrast, the results with chymotrypsinogen are time dependent and only partially reversible on release of the pressure. They involve conversion (tl/e = 5 min) to a form with a lower rotational rate at approximately 6 kbar and return to a fast-rotating form at higher pressure. This latter form persists on pressure release. The possibility of generating what are clearly metastable conformations, not only in chymotrypsinogen but also in flavodoxins [Visser, A. J. W. G., Li, T. M., Drickamer, H. G., & Weber, G. (1977) Biochemistry 16, 4879], indicates that there are unresolved questions about the relative stability of protein conformations which can be profitably investigated by high-pressure experiments.