The catalytic activity of thermolysin during the hydrolysis of N-(3-[2-furyl]acryloyl)-Gly-Leu amjde is noticeably enhanced in the presence of sugars and polyols. A series of polyhydroxylic additives were tested and the degree of activation was found to depend on both the concentration and nature of the additive. Sucrose and trehalose were found to yield the higher activation effect whereas glycerol was found to yield an inhibition of thermolysin in a large domain of concentration. A mechanism of activation based on the lowering of the energy barrier for the enzymatic reaction is proposed. This free energy barrier lowering is very likely due to water structure modification by the additives. (C) 1998 Elsevier Science Inc.