Large tetragonal hen egg white lysozyme single crystals (up to 16 mm(3)) can be obtained by the counter-diffusion method, using high concentration silica gels. The protein crystal lattice is able to incorporate large amounts of silica while still maintaining its short-range crystallographic order. The crystal morphology is controlled by the concentration of the silica gel, which can reduce surface energy anisotropy to such an extent that Spherical single crystals can be obtained as growth forms. The mechanical properties and the stability of the crystals against dehydration are improved by the incorporated hydrophilic silica polymeric network. This makes it possible to record full diffraction data sets with a resolution better than 1.5 Angstrom from crystals glued to glass fibers. Such reinforcement of the crystals facilitates their handling at ambient conditions and opens new possibilities for the measurement of physical properties of large biological macromolecules as well as for their technological applications.