Lipase-catalyzed alcoholysis between vinyl cinnamate and benzyl alcohol in fluorous solvents was investigated. This is the first report of a lipase-catalyzed reaction in a fluorous solvent. Forming the poly(ethylene glycol)(PEG)-lipase PL complex enhanced lipase activity over 16-fold over that of native lipase powder. The PEG-lipase PL complex exhibited markedly higher alcoholysis activities in fluorous solvents than in conventional organic solvents such as isooctane and n-hexane. The optimum reaction temperature for FC-77 (perfluorooctane) was 55 [degree]C and the optimum pH for the preparation of the PEG-lipase complex was 9.0; similar to the conditions for lipase PL-catalyzed reaction in aqueous solution. The alcoholysis reaction in fluorous solvent requires the addition of a FC77-miscible organic solvent (isooctane) in order to dissolve non-fluorinated substrates. Lipase activity in the fluorous solvent was significantly influenced by the volume ratio of isooctane in the reaction medium. Vinyl cinnamate inhibition of the lipase-catalyzed reaction occurred at a much lower concentration in the fluorous solvent than in isooctane. These results can be explained by the localization of substrates around lipase molecules, induced by adsorption of the substrates to the PEG layer of the PEG-lipase complex.