Attempts have been made to establish the level of immunoreactive corticotrophin (IR-ACTH) in serum in healthy subjects with partts were investigated and the clinical and biochemical condition s of selection specified. Serum IR-ACTH was determined by a radioimmunoassay procedure using an N-terminal antibody produced against the 1--24 sequence of the conrticotrophin molecule. The morning level of serum IR-ACTH was determined in 115 fasting healthy subjects, range less than 16--210 pg/ml, median 94 pg/ml (3rd International Standard preparation). The level was found to be unchanged within the age interval 20--94 years, irrespective of sex. Thy nycterohemeral variation of the IR-ACTH concentration in serum was studied in 11 sibjects. A rhythmic variation of the IR-ACTH level was not constantly found and age-related difference in the temporal pattern was not demonstrated. In 10 young and 10 elderly subjects a metyrapone test was carried out and the IR-ACTH response was determined. The rise in serum IR-ACTH concentration varied between 20 and 739 pg/ml. Any significant age-related difference in response was not found. The interpretation of the present results with respect to the decreased secretory activity of the glucocorticoid producing system in the aged is discussed. It was concluded that the findings in this study did not indicate a primary deficiency of the axis of the glucocorticoid producing system, neither at the pituitary level nor at the adrenocortical level, as a causal factor to the decreased glucocorticoid production in old age.