A study was carried out relating to the anticholinergic action of clonidine on the cardiovascular responses to i.c.v. injection of neostigmine, a quaternary anticholinesterase, in conscious sham-operated animals and rats with sinoaortic denervation, 7 days after the corresponding operation. Neostigmine (0.1-1 micrograms i.c.v.) induced a dose-dependent pressor and bradycardic responses in sham-operated rats but induced only an increase in blood pressure in sinoaortic-denervated animals. However, the pressor response in sinoaortic-denervated rats was significantly greater than in sham-operated animals. Clonidine (10 micrograms kg-1 i.v.) induced a fall in mean arterial pressure in sinoaortic-denervated rats but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. The anticholinesterase activity of clonidine (10 micrograms kg-1 i.v.), given 30 min previously, prevented the bradycardic action of neostigmine (0.1-1 micrograms i.c.v.) but failed to modify the pressor effect in sham-operated rats. This alpha2-adrenergic agent reduced the pressor response to i.c.v. administration of neostigmine in sinoaortic-denervated rats. Alternatively, the i.c.v. administration of clonidine (3 micrograms i.c.v.), given either 15 or 30 min before neostigmine, only prevented the bradycardic effect of the anticholinesterase (0.3 micrograms i.c.v.) in sham-operated rats but not the pressor action of this drug. In sinoaortic denervated rats, 3 micrograms of clonidine i.c.v. reduced an increase in blood pressure by i.c.v. injection of the anticholinesterase. The results suggest different central cholinergic mechanisms and different cholinergic-adrenergic interactions on the cardiovascular responses elicited by centrally injected neostigmine in sinoaortic denervated rats.