The NADP dependent enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) metabolizes glucocorticoids to their inactive Il-keto-metabolites in a wide range of tissues. To date very little is known about the regulation of this enzyme at the level of gene transcription. In this study we show significant changes in the uterine, renal, ovarian and hepatic levels of 11 beta HSD1 mRNA over the oestrous cycle. Uterine and renal message levels followed the same pattern, with the highest levels observed at dioestrus and the lowest levels at oestrus, a pattern that correlates with plasma oestrogen levels during the cycle. In both the uterus and kidney 11 beta HSD1 message levels more than halved from dioestrus to oestrus, while renal levels then doubled at metoestrus. In contrast, hepatic 11 beta HSD1 message levels at prooestrus were twice those observed at metoestrus. Ovarian levels remain constant until metoestrus when a marked decrease in message levels was seen. 11 beta HSD1 mRNA levels are thus differentially regulated in a tissue specific manner throughout the oestrous cycle.