A method for the synthesis and recovery from a Pichia pastoris yeast of a secreted, biologically active, heterologous (non-yeast) heteromultimeric immunoglobulin protein which is comprised of at least two non-identical subunit polypeptide chains, characterised by the following steps: (i) producing a stable diploidal Pichia pastoris yeast cell or cells by mating or spheroplast fusion of haploid Pichia pastoris yeast cells under conditions such that said mating or spheroplast fusion events result in the production of a diploid Pichia pastoris yeast cell or cells, wherein said diploid Pichia pastoris cell or cells after said mating or fusion comprise expression constructs that provide for the expression and secretion of the at least two non-identical polypeptide chains that constitute said heteromultimeric entire immunoglobulin protein, and which stable diploid Pichia pastoris yeast cells are capable of assembly and prolonged expression and secretion of said heteromultimeric entire immunoglobulin protein into a culture medium containing said stable diploid Pichia pastoris cell(s) when said diploid Pichia pastoris cell or cells are cultured under appropriate culture conditions; (ii) after effecting said mating or spheroplast fusion identifying and isolating the resultant diploidal Pichia pastoris cell or cells which contain expression constructs that provide for the stable expression and secretion of the at least two non-identical polypeptide chains that constitute said heteromultimeric entire immunoglobulin protein when said diploid Pichia pastoris yeast cell or cells are cultured under appropriate culture conditions; (iii) growing said isolated diploidal Pichia pastoris cell or cells or their diploid progeny in a culture medium under conditions that result in the expression, assembly and secretion of said biologically active heteromultimeric entire immunoglobulin protein into the culture medium; and (iv) recovering the resultant heteromultimeric protein from the culture medium; wherein said mating or spheroplast fusion is effected by mating or fusing a first yeast haploid Pichia pastoris cell containing a first expression construct, said first expression construct containing nucleic acid sequences encoding for the expression of at least one subunit of said heteromultimeric entire (intact) immunoglobulin protein, operably linked to a first yeast promoter; and a second Pichia pastoris haploid cell containing a second expression construct, said second expression construct comprising nucleic acid sequences encoding for the remaining subunit(s) of said heteromultimeric immunoglobulin protein, operably linked to a second yeast promoter. (i) producing a stable diploidal Pichia pastoris yeast cell or cells by mating or spheroplast fusion of haploid Pichia pastoris yeast cells under conditions such that said mating or spheroplast fusion events result in the production of a diploid Pichia pastoris yeast cell or cells, wherein said diploid Pichia pastoris cell or cells after said mating or fusion comprise expression constructs that provide for the expression and secretion of the at least two non-identical polypeptide chains that constitute said heteromultimeric entire immunoglobulin protein, and which stable diploid Pichia pastoris yeast cells are capable of assembly and prolonged expression and secretion of said heteromultimeric entire immunoglobulin protein into a culture medium containing said stable diploid Pichia pastoris cell(s) when said diploid Pichia pastoris cell or cells are cultured under appropriate culture conditions; (ii) after effecting said mating or spheroplast fusion identifying and isolating the resultant diploidal Pichia pastoris cell or cells which contain expression constructs that provide for the stable expression and secretion of the at least two non-identical polypeptide chains that constitute said heteromultimeric entire immunoglobulin protein when said diploid Pichia pastoris yeast cell or cells are cultured under appropriate culture conditions; (iii) growing said isolated diploidal Pichia pastoris cell or cells or their diploid progeny in a culture medium under conditions that result in the expression, assembly and secretion of said biologically active heteromultimeric entire immunoglobulin protein into the culture medium; and (iv) recovering the resultant heteromultimeric protein from the culture medium;