The stereospecific esterification of ibuprofen by Candida rugosa lipase (CRL) with 1-butanol was optimised. The yield of the butyl ester was nearly quantitative with an enantiomeric excess of 95% and E 100. Enzyme desiccation over P2O5 had a pronounced effect on the esterification yield and its role in stereospecificity is discussed. Molecular modelling and energy-minimisation studies were also performed to understand the stereospecific binding of substrates to the active site of CRL. The docking of the substrate S(+) ibuprofen to the active site of CRL was performed based on the three-dimensional structure of CRL (PDB entry 1CRL). The results show that only the active S(+) enantiomer of ibuprofen is able to form direct contacts with the reactive hydroxyl group (Ser209) and imidazole base (His449) at the active site, whereas with the R enantiomer the functional group COOH points away from the (His449) base of CRL. This is in accordance with experimental results which show that the stereospecifity of CRL is towards S(-) ibuprofen.