Continuous production of fatty acid methyl esters (FAMES) from corn oil was studied in a supercritical carbon dioxide (SC-CO(2)) bioreactor using immobilized lipase (Novozym 435) as catalyst. Response surface methodology (RSM) based on central composite rotatable design (CCRD) was employed to investigate and optimize the reaction conditions: pressure (11-35 MPa), temperature (35-63 degrees C), substrate mole ratio (methanol:corn oil 1-9) and CO(2) flow rate (0.4-3.6 L/min, measured at ambient conditions). Increasing the substrate mole ratio increased the FAME content, whereas increasing pressure decreased the FAME content. Higher conversions were obtained at higher and lower temperatures and CO(2) flow rates compared to moderate temperatures and CO(2) flow rates. The optimal reaction conditions generated from the predictive model for the maximum FAME content were 19.4 MPa, 62.9 degrees C, 7.03 substrate mole ratio and 0.72 L/min CO(2) flow rate. The optimum predicted FAME content was 98.9% compared to an actual value of 93.3 +/- 1.1% (w/w). The SC-CO(2) bioreactor packed with immobilized lipase shows great potential for biodiesel production. (C) 2011 Elsevier B.V. All rights reserved.