The aquaporin-2 promoter has been used to drive Cre recombinase expression in order to achieve renal collecting duct principal cell specific gene deletion. This technique requires two lines of mice: one transgenic mouse line containing a cell-specific promoter driving Cre recombinase expression and the other line, engineered using gene targeting strategies, that contains a lox-flanked target gene of interest. Mating of these two mouse lines permits cell-specific deletion of the target gene. This method could ultimately be used to obtain targeted deletion of any gene in any cell type in the kidney for which a specific promoter has been identified. The applications of this technology, as well as its strengths and weaknesses, are discussed with particular reference to the kidney.