Procedures are described for the crystallization of proteins, nucleic acids and viruses in a silica-gel matrix using otherwise standard reagents and conditions. Methods are given based on both vapor diffusion in a sitting drop and liquid-liquid diffusion. Using a variety of macromolecules our results suggest that the gel matrix suppresses nucleation, reduces the rate of growth, and generally leads to larger, higher-quality crystals of enhanced stability. Presumably these effects arise from the decreased mobility of the macromolecules and their flux at the crystal surface during growth.