The complete nucleotide sequence of the MEL1 gene of the yeast, Saccharomyces cerevisiae, encoding α-galactosidase was determined. The nucleotide sequence contains an open reading frame of 1413 bp encoding a protein of 471 amino acids. Comparison with the known N-terminal amino acid sequence of the mature secreted protein indicated that α-galactosidase is synthesized as a precursor with an N-terminal signal sequence of 18 amino acids. The general features of this signal peptide resemble those of other yeast signal peptides. Molecular weight of the mature α-galactosidase polypeptide deduced from the nucleotide sequence is 50.049 kd. The 5′ regulatory region has sequences in common with other yeast genes regulated by the GAL4-protein.