The enantioselective hydrolysis of racemic naproxen methyl ester by Candida rugosa lipase (CRL) was studied in aqueous buffer solution/isooctane reaction system in the presence of supercritical CO2. The effects pressure (75-160 bar), temperature (32-42 degrees C ) and reaction time (0.5-12 h) on the enantiomeric excesses of the product (ee(p)) and the substrate (ee(s)), enantiomeric ratio (E), conversion (x) and enzyme activity were investigated in a batch reactor system. The highest enantiomeric ratio achieved at 120 bar of pressure, 37 C of temperature and 2 h of reaction time was E= 193 with x=41.3%, ee(p)=97.9% and ee(s)=68.8%. CRL remained active at least for 12h at 37 degrees C and 120 bar in supercritical CO2 medium. Furthermore. enantiomeric ratio increased with increasing reaction time and reached the value of E=236 with ee(p) =98.2%, ee(s) =70.0% and x=41.6% after 12 h of hydrolysis. (C) 2007 Elsevier B.V. All rights reserved.