CGS19281A, a phenylethanolamine N-methyltransferase (PNMT) inhibitor, is reported not to inhibit α-2-adrenoceptor activity, in vitro. Effects of CGS19281A on the hypothalamic α-2-adrenoceptor function were studied in vivo in male Wistar rats. Agents used as controls were SKF2966l, which is a selective peripheral PNMT inhibitor, SKF64139, a PNMT inhibitor that inhibits equally both α-2-adrenoceptor activity and PNMT, and yohimbine, an α-2-adrenoceptor inhibitor that does not inhibit PNMT. Following the administration of PNMT inhibitors, hypothalamic 3-methoxy 4-hydroxy phenylglycol (MHPG) was measured during micro brain dialysis to observe its fluctuations. Effects of PNMT inhibitors on growth hormone (GH) secretion caused by clonidine were examined in order to assess the effects of PNMT inhibitors on postsynaptic α-2-adrenoceptors in the hypothalamus. Neither saline nor the peripherally active PNMT inhibitor SKF2966l (50 mg/kg) increased hypothalamic MHPG. Both SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) incresed MHPG significantly when compared with SKF2966l. There was no significant increase in MHPG after the administration of CGS19281A (20 mg/kg). Blood GH increased 30 min after clonidine was administered. While CGS19281A (20 mg/kg), SKF64139 (50 mg/kg) and yohimbine (5 mg/kg) inhibited GH secretion, the peripherally active PNMT inhibitor SKF2966l (50 mg/kg) did not. These results suggest that CGS19281A has an in vivo inhibitory effect on the clonidine induced GH secretion. This may be due to inhibition of adrenaline synthesis by this a