Amiloride-binding protein 1 (Abp1) is a diamine oxidase which catalyzes the breakdown of the polyamine putrescine. Putrescine is important for normal cell growth and proliferation, and elevated putrescine levels have been associated with certain tumors. Here we investigated the role of the Wilms' tumor gene product, Wt1, in the control of Abp1 expression. Wt1 protein functions as a transcription factor and tumor suppressor in the kidneys. Furthermore, Wt1 is necessary for normal embryonic development, particularly of the genitourinary system and mesothelial tissues, i.e. the epicardium. Silencing of Wt1 by RNA interference reduced Abp1 mRNA levels by approximately 60% in embryonic kidney-derived M15 cells. Conversely, Abp1 transcripts were increased more than threefold (n=5, P<0.05) upon induced expression of Wt1 in cultured cells. Luciferase reporter constructs carrying different Abp1 promoter sequences were stimulated several fold by co-transfection of a Wt1 expression construct. Interaction of Wt1 protein with the Abp1 promoter in cultured M15 cells in vivo was detected by chromatin immunoprecipitation (ChIP) analysis. Additionally, immunohistochemical staining revealed co-expressions of Wt1 and Abp1 in the epicardium of normal murine embryos at E11.5. Abp1 mRNA levels were significantly (n=5, P<0.05) reduced in the hearts of Wt1-deficient embryos compared to their wild-type littermates. These findings qualify the Wilms' tumor protein Wt1 as a novel transcriptional activator of the Abp1 gene in vitro and in vivo. It is suggested that stimulation of Abp1 expression by Wt1 has a role during normal embryogenesis and may also contribute to the suppression of tumor growth through regulating putrescine metabolism.