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The antihypertensive effects of Clonidine (0.15 mg kg−1, i.p.) were studied in conscious DOCA/saline hypertensive rats having chronically implanted arterial cannulae. The response to Clonidine was markedly reduced by simultaneously administered desipramine (3 mg kg−1, i.p.), antagonized dose-dependently by piperoxan (2–10 mg kg−1, i.v.) and prevented by pretreatment with phentolamine (0.2 mg, i.c.v.). Pretreatment with 6-hydroxydopamine (3 × 250 μg, i.c.v.), halo-peridol (1 mg kg−1, i.p.), p-chloro-N-methylamphetamine (3.5 mg kg−1, i.p.) or 5, 6-dihydroxytryptamine (50 μg and 25 μg, i.c.v.) did not significantly modify the antihypertensive response. It is concluded that the antihypertensive response to Clonidine is mediated via stimulation of central α-adrenoceptors and is independent of central dopaminergic receptors and intact central serotoninergic neurons. The necessity for intact central noradrenergic neurons remains uncertain.