Overexpression of protein disulfide isomerase (PDI) from a single chromosomally integrated copy in Saccharomyces cerevisiae results in ten-fold higher levels of secretion of human platelet derived growth factor B homodimer, and a four-fold increase in secretion of Schizosaccharomyces pombe acid phosphatase. This result provides evidence that inefficient protein folding limits the secretion of some heterologous proteins, and that manipulation of the endoplasmic reticulum lumenal environment can help overcome this limitation.