Abstract. The activation of mitogen-activated protein kinase (MAPK) pathways in the heart, for instance by 1-adrenoceptor agonists and endothelin-1, has primarily been associated with cellular growth regulation. Here we have investigated a possible role of MAPK pathways in the inotropic and chronotropic effects of adrenoceptor agonists and endothelin-1 in isolated rat left and right atria. Inotropic and chronotropic responses of the isolated atria to methoxamine, isoprenaline and endothelin-1 were measured in the absence and presence of inhibitors of MAPK pathways. The MAPK kinase (MKKmek) inhibitors PD98059 (100M) and U0126 (10M) significantly inhibited the inotropic responses to the 1-adrenoceptor agonist methoxamine (300M) and endothelin-1 (50nM), but not the chronotropic responses to these agonists. U0126 but not PD98059 inhibited the inotropic response to 3M isoprenaline. None of the aforementioned inotropic and chronotropic effects were inhibited by the MAPKPp38 inhibitor SB203580 (2M). We conclude that activation of the PD98059/U0126-sensitive MAPK pathway is essential for the inotropic but not chronotropic actions of adrenoceptor agonists and endothelin-1.