To study the relation of normetanephrine (NM) and metanephrine (M) to norepinephrine (NE) and epinephrine (E), plasma free NM (f-NM), free M (f-M), total NM (t-NM) and total M (t-M) were measured in normal subjects and patients with pheochromocytoma (PHEO), neuroblastoma, Cushing's syndrome, primary aldosteronism and chronic renal failure (CRF) by radioimmunoassay. Plasma f-NE and E were measured by radioenzymatic assay. Both f- and t-NM were high in PHEO, neuroblastoma and CRF. f- and t-M were also high in some patients with PHEO and CRF. Positive correlation was observed not only in f-NE with f-NM and t-NM, but also in f-E with f-M and t-M except for CRF. Although upright posture induced an elevation in f-NE and f-NM, t-NM was unchanged in normal subjects. In patients with PHEO, metoclopramide induced a prompt elevation in f-NE and E but no-change in t-NM and M levels. f-NE, f-E, f-NM, t-NM, f-M and t-M decreased rapidly after the resection of PHEO and reached the normal level on the third day after the surgery. In CRF patients, f-NM, t-NM, f-M and t-M decreased after hemodialysis despite an increase of f-NE. From these results, it was suggested that plasma NM and M levels reflected plasma NE and E to a certain extent in normal subjects and patients with normal renal function, and that the impaired renal function provoked an elevation of plasma NM and M due to the accumulation of them.