Cross-perfused canine atrial preparations were used to investigate the direct and indirect cardiac actions of clonidine and alinidine. Intravenous injections of clonidine (0.1-3 micrograms/kg) produced an initial brief pressor response and bradycardia followed by hypotension in the intact dog. Chronotropic and inotropic responses were absent in the isolated atrium perfused with the intact dog's blood. Intravenous clonidine (10-300 micrograms) also induced negative chronotropic and inotropic effects in isolated atria. On the other hand, alinidine, at doses which caused a depressor action and bradycardia in the intact dog, consistently produced negative chronotropic and inotropic effects in the isolated atrium. Therefore, it was confirmed that a relatively small dose of clonidine has a selective vascular action, while alinidine has direct cardiac depressant properties at all effective doses. Negative chronotropic and inotropic effects of peripheral vagal stimulation, carbachol and adenosine were not significantly modified by 100 or 300 micrograms doses of intraarterial clonidine. On the other hand, the effects of vagal stimulation and carbachol were significantly inhibited by 100 and 300 micrograms of alinidine, without affecting adenosine-induced cardiac actions. Therefore, it was demonstrated that alinidine has anti-muscarinic properties.