Human lysozyme (HLY) was successfully produced by Saccharomyces cerevisiae with a plasmid (pHK501) containing a synthetic HLY gene connected with a native secretion-signal sequence under control of the promoter for the glyceraldehydes-3-phosphate dehydrogenase gene. For large-scale production, batch fermentation was adopted with 1 l SD (Leu(-)) minimal medium in a 2-l jar fermentor. While pH-uncontrolled fermentation gave 42.3 units/ml of HLY over a period of 72-h cultivation, HLY production increased to 74.5 units/ml by performing pH-controlled fermentation, although a longer fermentation time was needed for maximal HLY production. A pH-shift strategy was designed in this study, resulting in higher HLY production and a shorter fermentation time.