To evaluate the role of sexually dimorphic tissue expression of 11β-oxidase activity of 11β-hydroxysteroid dehydrogenase (11βHSD) in gender-associated blood pressure differences, we have studied female and male hypertensive rats of two different strains and their normotensive controls: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and Dahl salt-sensitive (SS/Jr) and salt-resistant rats (SR/Jr). In hypertensive SHR and SS/Jr, but not in normotensive strains WKY and SR/Jr, blood pressure reached a higher level in males than in females. The activity of 11βHSD was higher in the renal cortex, medulla, colon and aorta of males than of females in all investigated strains with the exception of aortic 11βHSD in SHR and WKY rats, both of which had very low 11β-oxidase activity. In contrast to gender-dependent differences, strain differences of 11βHSD were observed in a limited number of tissues only. Renal medullary 11βHSD showed significantly lower activity in WKY than in SHR, whereas no difference was observed in the renal cortex. Similarly, colonic 11βHSD activity was lower in WKY than in SHR. In Dahl rats the strain differences were observed in aortic 11βHSD that had higher activity in SR/Jr than in SS/Jr rats; no difference was observed in the kidney or colon. These data demonstrate the following. 1) Sexual dimorphism of 11βHSD activity exists in the kidney, colon, and aorta. 2) The sexual dimorphism of 11βHSD does not play a role in gender-associated differences in blood pressure. 3) The reduced 11βHSD activity in the aorta of hypertensive SS/Jr compared to SR/Jr rats suggests that this enzyme might play a role in the pathogenesis of salt-sensitive hypertension in Dahl rats. (Hypertens Res 2003; 26: 333-338)