The polyhedral (in-)stability of monoclinic hen-egg white lysozyme (HEWL) crystals, grown by means of PEG-6000, and that of orthorhombic trypsin crystals has been investigated experimentally. On the basis of a quantitative theoretical analysis, it is compared with the polyhedral (in-)stability of tetragonal HEWL and cubic ferritin crystals. The unambiguous conclusion is that the phenomenon is due to the diffusive supply of matter. This conclusion is also supported by the fact that the phenomenon has common features for both proteins and small molecular crystals. (C) 2002 Elsevier Science B.V. All rights reserved.