We studied secretory activity of the adrenal gland by determining cortisol blood levels throughout a 24-h cycle at 2-h intervals in 26 patients with rheumatoid arthritis (RA), not previously treated with glucocorticosteroids or disease modifying drugs. In patients with low erythrocyte sedimentation rates [(ESR) up to 40 mm/h] and medium disease activity (ESR between 40 and 80 mm/h), cortisol maxima and minima shifted to earlier times of the day whereas in patients with high activity (ESR higher than 80 mm/h) the circadian rhythm was lost or markedly reduced. The inflammatory activity of the RA significantly correlated with the adrenal cortisol secretion (linear regression analysis between ESR and the arithmetic mean value of cortisol throughout a 24-h cycle with a coefficient of regression r = 0.63, n = 26, p less than 0.001). The influence of mediators of inflammation, such as interleukin 1, on hypothalamic centers, stimulating the hypothalamus-pituitary-adrenal axis, is discussed.