The hemodynamic effects of the low K , CAMP peak Ill PDE inhibitor medorinone (0.01-0.3 mglkg, i.v.) were evaluated in anesthetized dogs in the presence and absence of p-adrenoreceptor blockade. Medorinone increased the peak derivative of left ventricular pressure (+dP/dt) in non-blocked (all doses) and p-blocked dogs (20.03 mg/kg) (2,766t259 and 1,403~262 mm Hg/sec, respective max. changes). Heart rate (HR) was increased by medorinone in non-blocked (20.1 mg/kg) and p-blocked dogs (20.03 mgikg) (77.458.9 and 25.5t4.3 beatshin, respective max. changes). In non-blocked dogs only, medorinone (all doses) decreased left ventricular end-diastolic pressure (LVEDP) (7.7t1.7 mm Hg, max. change). Mean arterial pressure (MAP) was similarly decreased by medorinone (20.03 mg/kg) in p-blocked and non-blocked dogs (max. approx. -27 mm Hg). Medorinone did not affect cardiac output or renal blood flow. The hemodynamics of medorinone and milrinone (another peak Ill PDE inhibitor) in non-blocked dogs were similar, except medorinone was less potent in increasing +dP/dt (2,766t259 vs. 3,747k388, max. changes) and more potent in reducing LVEDP (-7.721.7 vs. -1.8k1.2 mm Hg, max. changes). In conclusion, medorinone similarly reduced MAP, but more effectively decreased preload, increased inotropy and chronotropy in non-blocked than p-blocked anesthetized dogs. Medorinone is more potent in reducing preload, but less potent in enhancing inotropy when compared to milrinone in anesthetized dogs.