The major site of cortisol metabolism in man has been thought to be the liver. Studies in patients with either congenital or acquired deficiency of 11 beta-hydroxysteroid dehydrogenase (an enzyme responsible for the interconversion of cortisol to cortisone) suggested that the kidney was an important site of cortisone production. In 88 patients with proven renal disease but normal liver function, arbitrarily divided into four groups on the basis of plasma creatinine, 0900 h plasma cortisone was significantly reduced in all groups when compared with 47 controls (e.g. 21 +/- 3 nmol/l (mean +/- SEM) in patients with plasma creatinine greater than 0.45 mmol/l vs 62 +/- 3 nmol/l in controls, P less than 0.001). 0900 h plasma cortisol was not significantly different. There was an inverse correlation between plasma creatinine and plasma cortisone (r = -0.55, p less than 0.01). Four anephric patients had a 0900 h plasma cortisone level of 6 +/- 1 nmol/l. We conclude that the kidney is a major site for the conversion of cortisol to cortisone and hence cortisone production in man. The relevance of this to the pathophysiology of salt and water metabolism in renal disease remains to be elucidated.