1 To date no study has described the cardiovascular e ects of increased myo®lament Ca 2+ responsiveness in awake animals both under resting conditions and during treadmill exercise. In the present study we therefore investigated the systemic, pulmonary and coronary haemodynamic actions of the Ca 2+ sensitizer EMD 57033 in 16 chronically instrumented awake pigs at rest and during treadmill exercise, and compared these to the haemodynamic actions of the Ca 2+ sensitizer/phosphodiesterase inhibitor pimobendan. 2 Under resting conditions EMD 57033 (0.2, 0.4 and 0.8 mg kg 71 min 71 , i.v.) produced dosedependent increases in LVdP/dt max (up to 65+17% (mean +s.e.mean), P40.05) and stroke volume (up to 20+3%, P40.05), with an increase in heart rate only after the highest dose (22+5%, P40.05), while mean aortic blood pressure and LVdP/dt min were not altered. EMD 57033 had also no e ect on pulmonary vascular resistance, but produced dose-dependent decreases in systemic vascular resistance (32+4%, P40.05), and coronary vascular resistance (44+2%, P40.05). These e ects were essentially unchanged when animals were pretreated with non-selective b-adrenoceptor blockade, indicating that phosphodiesterase inhibition did not contribute to the positive inotropic actions of EMD 57033. 3 During exercise at 2, 3, and 4 km h 71 , the positive inotropic actions of EMD 57033 gradually waned at higher levels of exercise. This may have been caused by the exercise-induced increase in b-adrenergic activity, because after pretreatment with propranolol the positive inotropic actions of EMD 57033 were preserved at all levels of exercise. In contrast, the positive inotropic and chronotropic e ects of pimobendan were ampli®ed during exercise, but were abolished (at rest) or markedly attenuated (during exercise) after pretreatment with propranolol. 4 The responses to EMD 57033 during exercise after combined a-and b-adrenergic receptor blockade were not di erent from those after b-adrenergic receptor blockade alone, indicating that the positive inotropic actions of EMD 57033 were not mediated via or did not depend on intact a-adrenergic receptor activity. 5 In conclusion, EMD 57033 increases left ventricular myocardial contractility in awake pigs. During exercise this e ect is partially o set by the increased b-adrenergic activity, with no e ect of a-adrenergic activity, suggesting that EMD 57033 may be most e ective in patients with severe loss of b-adrenergic responsiveness.