1. 11-beta-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11 beta-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11 beta-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex. 2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11 beta-dehydrogenase (as measured by a rise in the plasma half-life of [11 alpha-3H]cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate). 3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11 beta-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.