5-hydroxytryptamine (5-HT), from the concentration of 5 microM to 50 microM has a positive chronotropic activity on the rat isolated atria. The tyramine-like indirect sympathomimetic effect is the main mechanism of the 5-HT action at high concentration (50 microM). In this study, we have demonstrated that 5-HT2 receptor stimulation is also involved in the 5-HT-induced increase in atrial rate. Thus, when the tyramine-like effect was inhibited by reserpine, which causes a noradrenaline depletion of atria, the positive chronotropic effect of 5-HT (50 microM) was reduced but not abolished. The remaining response to 5-HT was completely inhibited by the 5-HT2 antagonist ketanserin (1 microM). Moreover, the increase in atrial rate induced by 5-HT, at the lower concentration of 5 microM, was fully abolished by this antagonist.