Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare disorder, transmitted as an autosomal dominant trait, characterized by polyuria and polydipsia, and caused by deficient neurosecretion of arginine vasopressin precursor (AVP-NPII). More than 40 mutations have been described since the first mutation of AVP-NPII gene was reported in 1991. We diagnosed two families with ADNDI and identified a 3 bp deletion (1827-1829delAGG) of AVP-NPII gene in one pedigree. We found no mutations in the coding, the promoter and intronic regions of AVP-NPII gene in the other ADNDI family. A genome-wide scan was performed in this family and the maximum LOD score of 1.202999( = 0.00)was obtained at marker D20S889. Fine mapping localized the corresponding gene(s) in a 7 cM interval defined by D20S199-D20S849 on Chromosome 20, in which AVP-NPII gene is also located. We further sequenced the intragenic region (IGR) that regulates AVP-NPII and oxytocin expression as an enhancer element and UBCE7IP5 gene that participates in prohormone degradation, and did not detect any alterations for those candidate genes. Regarding the almost identical clinical features in these two families, the corresponding locus responsible for ADNDI is possibly heterogeneous.