The cardiovascular effects of tyramine, and its interactions with propranolol, atenolol, phentolamine, prazosin, yohimbine and atropine, have been investigated in anesthetized rats in vivo and in vitro. Tyramine (i.v.) increased both the mean arterial blood pressure and heart rate. Phentolamine, prazosin or a combination of prazosin and yohimbine caused an inhibition of the hypertensive effect of tyramine, but propranolol, atenolol and/or atropine had no effect. Propranolol added to rats receiving atropine depressed the chronotropic effect of tyramine. However, in non-atropinized animals, the positive chronotropic effect of tyramine was paradoxically enhanced by propranolol, and further enhanced by atropine. A similar result was found with atenolol pre-treated animals. Phentolamine did not alter the effects of propranolol and atropine on heart rate. Prazosin depressed the positive chronotropic effects of tyramine, and this effect was re-stored by pre-treatment of the animals with both prazosin and yohimbine. In the isolated atria, propranolol--in contrast to the in vivo results--inhibited the chronotropic effect of tyramine. Atropine potentiated the positive inotropic effect of isoproterenol and tyramine. Tyramine produced a concentration-dependent contraction of isolated thoracic aortic rings, and this was potentiated by N(G)-nitro-l-arginine, or by removal of the endothelium, but inhibited by phentolamine. The in vivo and in vitro effects of tyramine were not seen in rats which had been treated with reserpine. We conclude that the positive inotropic and chronotropic effects of tyramine in the rat are due to indirect release of transmitter. The results suggest that the paradoxical enhancement by propranolol and atenolol of the chronotropic effect in vivo could be due to tyramine causing increased vagal activity, such that an inhibitory effect of propranolol can only be revealed in animals treated with atropine.