This study examines the in vivo effects of 2,3-dichloro-α-methylbenzyl-amine (DCMB), a centrally active phenylethanolamine-N-methyltransferase (PNMT) inhibitor, on α2-adrenoceptors. Sixty-six rats received either DCMB, SKF2966l, the peripheral PNMT inhibitor, at a dose of 50 mg/kg or saline intraperitoneally. To examine the functional responses of the α2-adrenoceptors to these drugs, changes in spontaneous locomotor activity, concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) in dialysates from the hypothalamus, and the influence of clonidine on growth hormone (GH) secretion were investigated. (1) DCMB increased spontaneous motion of the rat. (2) DCMB increased extracellular MHPG concentration in the hypothalamus verified by micro-brain dialysis. (3) Clonidine failed to stimulate GH secretion in DCMB-treated rats. These results suggest that DCMB has an inhibitory action on the α2-adrenoceptor function in v