BACKGROUND: Sol-gel entrapment of lipases is usually performed in an aqueous solution. A novel method of sol-gel coating of lipase in supercritical carbon dioxide (SC-CO2) is proposed. RESULTS: Crude lipase powder (Rhizopus oryzae) coated with hydrophobic silicates, derived from dimethyldimethoxysilane and tetramethoxysilane in SC-CO2 at 35 degrees C and 15 MPa, exhibited 5-7 times higher esterification activity than that prepared via an aqueous sol-gel route. Lipase immobilized in a methyl-substituted silica monolith was also highly activated by sol-gel coating using the same silica precursors in SC-CO2. CONCLUSION: Sol-gel coating in SC-CO2, of lipases in powder and immobilized forms with hydrophobic alkyl-substituted silicates provides an efficient tool for the enhancement of enzymatic activities in non-aqueous media. (c) 2009 Society of Chemical Industry