Glucocorticoids influence the function of numerous tissues. Although there are a very large number of studies that have investigated the local metabolism of glucocorticoids in mammals, the knowledge of this metabolism in birds is limited. The local concentration of corticosterone is critical for both glucocorticoid- and mineralocorticoid-dependent activity, and we have therefore carried out studies of corticosterone metabolism in various chicken organs. It was found that corticosterone was metabolized to 20-dihydrocorticosterone, and in some tissues also to 11-dehydrocorticosterone and 11-dehydro-20-dihydrocorticosterone. The activity of 20-hydroxysteroid dehydrogenase (20HSD), responsible for the transformation of corticosterone to 20-hydroxy derivatives, was abundant in the kidney and intestine, with lower levels in the liver and testis. Low levels of 20HSD were detected in the brain and ovaries. In contrast, 11-hydroxysteroid dehydrogenase (11HSD) activity was only found in the kidney and intestine. No activity was observed in the brain, testis, or ovaries. The treatment of chickens with estrogens stimulated 20HSD activity in the kidney, intestine, and oviduct and 11HSD activity in the liver and oviduct. Kinetic studies for corticosterone yielded an apparent Km for 11HSD in the nanomolar (Km = 21 +/- 5 nmol.l(-1)) and for 20HSD in the micromolar range (Km = 3.7 +/- 0.3 micromol.l(-1)). When progesterone or 5alpha-dihydrotestosterone were used instead of corticosterone, the tissues reduced the former to 20beta-dihydroprogesterone and the latter to both 5alpha,3alpha- and 5alpha,3beta-dihydrotestosterone. The data presents the first evidence for corticosterone metabolism via 11beta-, 3alpha/3beta-, and 20beta-hydroxysteroid dehydrogenases in various chicken organs and provide support for the theory of prereceptor modulation of glucocorticoid signals in avian tissues.