The effects of oleuropeoside were studied on the electromechanical properties of isolated guinea-pig atria. In spontaneously beating right atria, oleuropeoside decreased the amplitude of contractions (IC50 = 1.3 +/- 0.2 x 10(-4) M), slightly decreased atrial rate, and lengthened sinus node recovery time. Oleuropeoside also inhibited peak contractile force in electrically driven left atria incubated in normal (IC50 = 1.5 +/- 0.5 x 10(-4) M) and in 27 mM K+ Tyrode solution (IC50 = 1.7 +/- 0.4 x 10(-4) M). These negative inotropic effects were not accompanied by significant changes in the characteristics of action potentials recorded in atria incubated in either normal or depolarizing solutions. These results indicate that oleuropeoside produced an electromechanical uncoupling that cannot be attributed to an inhibitory effect on Ca2+ entry through L-type channels. Therefore, the negative inotropic effect may reflect an action of oleuropeoside perhaps at an intracellular level.