The effects of short-term lithium (Li) administration on alpha 2-adrenoceptor sensitivity was studied in 10 healthy volunteers and in 15 patients with normothymic, phasic depressive disorders. The GH-clonidine test was used to examine alpha 2-adrenoceptor sensitivity, administered before and after Li treatment (600 mg/day for 7 days in controls and for 15 days in patients). Before treatment, the GH response to clonidine in the patients was blunted, and afterwards it tended to increase in the patients and it was significantly decreased in the controls. The difference between the response in the two groups was significant and was correlated both with the diagnosis and the pretreatment GH response to the stimulus. The opposing pattern of the response in patients and controls to Li administration suggests that the drug exerts a modulatory effect on alpha 2-adrenoceptor sensitivity, with up or down regulation inversely correlated with pretreatment status.