Administration of clonidine produced biphasic changes in the type II inhibitor activity (endogenous inhibitor of protein kinases which specifically regulates phosphorylation mediated by cGMP-dependent system). Small doses of clonidine (10-50 micrograms/kg) produced an increase while large doses (200-1000 micrograms/kg) induced a decrease in the type II inhibitor activity. The both actions of clonidine were greatly reduced in vasopressin hypertensive rats suggesting subsensitivity of alpha 2-adrenergic receptors. Subsensitivity of postsynaptic alpha 2-receptors was also observed in anterior hypothalamus in in vitro experiments. Incubation of anterior and posterior hypothalamic slices with clonidine resulted in concentration-dependent increase in cGMP content and a decrease in the type II inhibitor activity. The clonidine action in anterior hypothalamus of vasopressin-hypertensive rats was greatly reduced. In contrast, the clonidine action in posterior hypothalamus was the same in vasopressin-hypertensive as in the control rats.