BACKGROUND: Hexyl laurate has been applied widely in cosmetic industries and is synthesized by chemical methods with problems of cost, environmental pollution, and by-products. In this study, Lipozyme (R) IM77 (from Rhizomucor miehei) was used to catalyze the direct-esterification of hexanol and lauric acid in a solvent-free system by utilizing a continuous packed-bed reactor, wherein the aforementioned difficulties could be overcome. Response surface methodology (RSM) and three-level-three-factor Box-Behnken design were employed to evaluate the effects of synthesis parameters, such as reaction temperature (45-65 degrees C), mixture flow rate (0.25-0.75 mL min(-1)) and concentration of lauric acid (1100-300 mmol L-1) on the production rate (mu mol min(-1)) of hexyl laurate by direct esterification. RESULTS: The production rate was affected significantly by the mixture flow rate and lauric acid concentration. On the basis of ridge-max analysis, the optimum synthesis conditions for hexyl laurate were as follows: 81.58 +/- 1.76 mu mol min(-1) at 55 degrees C, 0.5 mL min(-1) flow rate and 0.3 mol L-1 lauric acid. CONCLUSION: The lipase-catalyzed synthesis of hexyl laurate by Lipozyme (R) IM-77 in a continuous packed-bed bioreactor and solvent-free system was successfully developed; optimization of the reaction parameters was obtained by Box-Behnken design and RSM. (C) 2008 Society of Chemical Industry