The positive chronotropic effect of a high concentration of 5-hydroxytryptamine (5-HT) in rat isolated atria results mainly from a tyramine-like mechanism and is linked to an increase in cAMP production by an indirect stimulation of beta-adrenoceptors. Using this preparation, we have compared the action of tyramine and 5-HT. The tyramine (0.15 microM)-induced increase in atrial rate was suppressed by atenolol (a beta 1-blocking drug) and by nadolol (a beta 1 beta 2-blocker), while the positive chronotropic effect of 5-HT was reduced by atenolol and suppressed by nadolol. The 5-HT-induced elevation in cAMP was unchanged in the presence of atenolol and abolished by nadolol. The involvement of beta 2-adrenoceptors in the effects of 5-HT could result from competition between 5-HT and noradrenaline at the beta 1-adrenoceptors that results in a fixation of noradrenaline on beta 2-adrenoceptors.