Here we describe the generation and characterization of a mouse strain that expresses an improved Cre (iCre) recombinase (48) under the control of the endogenous 11beta-hydroxysteroid dehydrogenase type 2 (11HSD2) promoter. Progeny of 11HSD2/iCre and ROSA26 reporter mice were used to determine the pattern of iCre expression by measuring the activity of the LacZ gene product beta-galactosidase in a panel of tissues. On Cre recombinase activity, intense beta-galactosidase activity (X-gal staining) was observed in the classic mineralocorticoid target segments of the kidney, as well as in the colon, and both female and male reproductive organs. Weaker iCre expression was detected in the lung and heart. In the brain, strong iCre activity was present in cardiovascular centers that are known to express 11HSD2 and mineralocorticoid receptors [nucleus tractus solitarius (NTS) and amygdala] as well as in the granular layer of the cerebellum. iCre expression was weaker in neonatal kidney and colon than in the adult but was present in the hair follicles and cartilage. These results indicate that in the 11HSD2/iCre strain iCre expression faithfully represents the expression pattern of endogenous 11HSD2. Thus this mouse model represents the first Cre deleter strain that can be used to eliminate desired genes in every mineralocorticoid target tissue. This mouse model should serve as a useful resource for investigators who want to study the function of genes involved in aldosterone action and genes in other pathways that are selectively expressed in these cells.