To examine the noradrenergic function in endogenous depression, binding of a selective agonist radioligand, H-3-UK 1 4304, to platelet alpha-2-adrenergic receptors and plasma free 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in untreated depressed patients. The effects of an antidepressant, mianserin, on these parameters were also assessed. The B(max) and K(d) values for H-3-UK 14304 binding in 26 untreated depressed patients were significantly higher (p < 0.05, p < 0.01) than those in 26 normal controls. On the other hand, there were no significant differences in plasma free MHPG levels between 12 untreated depressed patients and 12 normal controls. Chronic administration of mianserin to 8 depressed patients slightly increased the B(max) and K(d) values. However, plasma free MHPG levels did not change after treatment. These findings suggest that depression is related to the subsensitivity of alpha-2-receptors as indicated by a decreased affinity of platelet alpha-2-receptors. In addition, chronic administration of mianserin further decreased the affinity of alpha-2-receptors. This suggests that mianserin acts not only on alpha-2-receptors but also on the other neurotransmitter systems.