Results of routine methods for measurements of plasma cortisol and his urinary metabolites have been comparated with those of cortisol secretion rate (CSR) measured by simple isotopic dilution; the latter appears for his specify and precision, to be the most suitable for an exact evaluation of cortisol production by the adrenals. In normal subjects CSR resulted slightly lower than those reported in the literature; in obese subjects CSR was slightly higher than in normals, also when it was related to the urinary creatinine. In the patients with Cushing's syndrome, CSR was considerably higher, with no overlap with the obese subjects. The CSR was also useful in showing values lower than normal, in hypopituitarism, and in confirming hormone abnormal findings in thyroid diseases.