• We measured plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) in 13 pairs of healthy drug-free monozygotic twins. High concordance for both free and conjugated MHPG suggests that plasma levels of the metabolite may reflect a heritable biological trait. In two drug-free rapidly cycling patients studied longitudinally, plasma MHPG levels reflected alterations in psychiatric state; they were significantly higher during mania than during depression. Although largely reflecting peripheral sources, plasma MHPG level as a global index of noradrenergic function may complement urinary MHPG excretion as a probe for diagnostic subgroups or pharmacologic responsiveness in psychiatric research.