Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (FV) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephrine (NE) in CS, Ao and FV were 359±49 (SEM) pg/ml, 290±27 and 234±24, respectively. The corresponding values of epinephrine (E) were 127±18 pg/ml, 186±30 and 97±11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p<0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate significantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in Ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.