We recently reported evidence of a novel type 2 diabetes locus placed on chromosome 12q15 between markers D12S375 and D12S1684 (Diabetes 48:2246-2251, 1999). Four multigenerational families having logarithm of odds (LOD) scores >1.0 in the original analysis were genotyped for 11 additional markers in this interval to refine this mapping; this allowed us to narrow the linked region to the interval between markers D12S1693 and D12S326. In a multipoint parametric analysis using the VITESSE software, the LOD score for linkage at this location reached 3.1 in one of these families. This interval contains the gene for protein tyrosine phosphatase receptor type R (PTPRR)--a protein that may be involved in both insulin secretion and action. After determining PTPRR exon-intron structure, we identified several polymorphisms in this gene but no mutation segregating with diabetes. The search for mutations was also negative for carboxypeptidase M (CPM)--another candidate gene mapped to this region. In summary, our data provide further evidence for the existence of a type 2 diabetes locus on chromosome 12q15. This locus, however, does not appear to correspond to the PTPRR or CPM, although a contribution of mutations in regulatory regions cannot be excluded at this time.