The sequence of studies leading to the assignment of the locus for multiple endocrine neoplasia (MEN2A) to chromosome 10 are described. They began with the exclusion of linkage between the disease locus and loci for conventional markers and a deletion site reported to be associated with the disease on chromosome 20. After 32% of the genome had been excluded, a "hint" of linkage was found but considerable additional family data were necessary in order to establish linkage to the marker locus D10S5. The DNA marker D10S5 was assigned to chromosome 10 by in situ hybridization and tests of linkage between the marker and disease loci were significant. The assignment of the marker and the linkage implied that the disease gene was on chromosome 10. The assignment was confirmed by the demonstration of an additional linkage, between the disease locus and the gene for interstitial retinol binding protein (RBP3) that had also been assigned to chromosome 10. Closer and flanking markers are now being sought as steps to providing better than Mendelian risks for the MEN2A genotype and for the ultimate identification of the gene.