The tissue-specific transcription factorsHNF1aandHNF1b are closely related homeodomain proteins conserved in vertebrate evolution. Heterozygous mutations in human HNF1b 1 but not inHNF1agenes are associated with kidney malformations. Overexpression of HNF1b in Xenopus embryos leads to defective pronephros development, while HNF1ahas no effect. We have defined the regions respon-sible for this functional difference between HNF1band HNF1ain transfected HeLa cells as well as in injected Xenopusembryos. .