The aim of this study was to synthesize human milk fat substitute (HMFS) enriched with medium-chain fatty acids (MCFAs) by Lipozyme(R) RM IM-catalyzed acidolysis. The reaction substrates (tripalmitin, hazelnut oil fatty acids and Neobee(R) fatty acids) were specially chosen to mimic human milk fats and to enrich HMFS with MCFAs. Substrate molar ratio, reaction temperature and enzyme content were used to model and to optimize the reaction conditions via response surface methodology. The experiment was carried out at the optimal condition generated from the model yielded structured lipids with caprylic acid (12.8 g/100 g), capric acid (10.6 g/100 g) and palmitic acid (30 g/100 g). These values were found similar to the values predicted by the model (15.9 g/100 g, 14.1 g/100 g and 33.3 g/100 g). It can be concluded that the potential use of the structured lipids (SLs) produced in infant formulas provide energy source delivering a reduced calorie value for newborn, term and preterm infants. (C) 2010 Elsevier Ltd. All rights reserved.