This chapter reviews the expression of two proteins that are naturally secreted: murine epidermal growth factor (mEGF) and the 120-kDa envelope protein from human immunodeficiency virus (HIV-1 ENV). Although the initial aims of these projects were to examine the secretion inPichia pastorisof a simple polypeptide and a complex glycoprotein, ultimately the work yielded insights into a wide range of issues affecting gene expression inP. pastoris, from foreign gene transcription to multicopy selection and glycosylation.