A recombinant human $alpha_{s1}$-casein was expressed as a secretory product in the yeast Saccharomyces cerevisiae. Three different leader sequences derived from the mating factor $alpha$l (MF$alpha$l), inulinase, and human $alpha_{s1}$-casein were used to direct the secretion of human $alpha_{s1}$-casein into the extracellular medium. Among the three leader sequences tested, the native leader sequence of human $alpha_{s1}$-casein was found to be the most efficient in the secretory expression of human $alpha_{s1}$-casein, which implies that the native leader sequence of human $alpha_{s1}$-casein might be used very efficiently for the secretory production of other heterologous proteins in yeast. The recombinant human $alpha_{s1}$-casein was proteolytically cleaved as the culture proceeded. Therefore, an attempt was made to produce human $alpha_{s1}$-casein using a S. cerevisiae mutant in which the YAP3 gene encoding yeast aspartic protease 3 (YAP3) was disrupted. After 72 h of culture, most of the human $alpha_{s1}$-casein secreted by the wild type was cleaved, whereas more than 70% of the human $alpha_{s1}$-casein secreted by yap3-disruptant remained intact. The results suggest that YAP3 might be involved in the internal cleavage of human $alpha_{s1}$-casein expressed in yeast