A gene fusion consisting of 960 base pairs of 5′-flanking region of the yeast MF αl gene, 257 base pairs coding for α-factor prepro sequence, and a modified human IFN-αl gene was constructed. MAT α cells containing the chimeric gene synthesized and secreted active IFN-αl into the growth medium. The secreted interferon molecules contained the last 4 amino acids of α-factor prepro sequence and the amino acids encoded by the DNA modifications introduced at the beginning of IFN-αl gene. DNA sequences coding for these amino acids were removed by oligonucleotide-directed in vitro mutagenesis. Yeast cells transformed with expression plasmids containing the altered junction synthesized and secreted human IFN-αl with the natural NH ₂ -terminus.