SUMMARY The plasma immunoreactive corticotrophin (ACTH) response to metyrapone (1 g orally at 08.00 h, and 6 hourly thereafter for 48 h) was analysed in 20 patients with a normal oxogenic steroid response. A greater than threefold rise in the mean plasma ACTH concentration was observed within 24 h. The mean plasma ACTH level at 08.00 h on the 2nd day of the test was significantly higher than the mean level at 16.00 h, indicating that the diurnal rhythm in ACTH release persists despite metyrapone administration. The degree of rhythmicity, as assessed by the ratio of the means of the 08.00 and 16.00 h ACTH values on the 2nd day of metyrapone administration, was comparable to, but slightly less than that observed in untreated normal controls. The ACTH response to reduction of circulating cortisol levels was also studied by interrupting steroid replacement therapy for 24 h in eight patients with adrenal disease. The observed increase in plasma ACTH was more variable than that after metyrapone, the rapidity of the ACTH rise possibly being influenced by the details of previous replacement therapy and the severity of the adrenal disease. There was no significant difference in the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia in 13 patients whose pituitary function had been assessed by each of these procedures.