THE matine-tvoe locus (MAT) encodes several DNA-bindine proteins, which determine the three cell types of Saccharomyces cerevisiae: the a and α haploid cell types, and the a/α diploid cell type1. One of the products of MAT, α2, functions in two cell types. In α cells, α2 represses the a-specific genes by binding to the operator as a dimer2. In a/α diploid cells, α2 acts with al, a product of the other MAT allele, to repress a different set of genes, the haploid-specific genes3,4. Until now, the nature of the interaction between al and α2 was not known, although it had been suggested that α2 may form a heterodimer with al (ref. 5). I show, by using proteins synthesized in vitro, that al and α2 bind the operator of a haploid-specific gene as a heterodimer. The ability of α2 to form both homodimers and heterodimers with al, each with a different DNA-binding specificity, explains the dual regulatory functions of α2. This is the first example of regulation by heterodimerization among homeobox-containing proteins, a class that includes proteins responsible for the specification of segment identity in Drosophila, mammals and other eukaryotes. © 1990 Nature Publishing Group.