Human lipocortin-I was very efficiently produced as a secretory product by Saccharomyces cerevisiae harbouring an optimized expression casette containing the GAL10 promoter, inulinase signal sequence and the lipocortin-I terminator. To overproduce lipocortin-I, a fed-batch fermentation was performed. The feed medium contained only glucose as sole carbon source and was first fed for cell growth. A mixture of glucose and galactose was then fed for gene induction in parallel with cell growth. During the gene induction period, a significant amount of lipocortin-I accumulated in the culture medium. However, about 45% of the secreted lipocortin-I existed in a proteolytically-cleaved form, cleaved after the basic amino acid Lys(26). At the end of the culture, the concentration of total extracellular lipocortin-I (intact form + cleaved form) was about 2.1 g/l, accounting for more than 80% of the total extracellular protein.