Background. Some clinical and experimental studies suggest that propofol decreases myocardial contractility and relaxation, whereas others report preserved cardiac function. To investigate the effects of propofol on intrinsic contractility and relaxation, increasing concentrations of propofol were infused in isolated blood-perfused rabbit hearts. Equimolar concentrations of thiopental were infused as a reference group. Methods. Coronary blood flow, left ventricular contractility and relaxation (as maximal positive and negative left ventricular pressure derivatives [dP/dt(max) and dP/dt(min)], respectively), and myocardial oxygen consumption (MvO2) were measured during infusion of 10-1,000 muM propofol in blood-perfused hearts. To determine whether the effects of propofol depend on the heart's perfusate, propofol also was infused in isolated buffer-perfused rabbit hearts. In addition, the effects of propofol solvent were investigated in blood- and buffer-perfused preparations. Results. In blood-perfused preparations, coronary blood flow increased with propofol concentrations greater than 30 mum and with 300 and 1,000 mum thiopental. Left ventricular dP/dt(max) and dP/dt(min) remained unchanged with propofol and decreased with concentrations of thiopental equal to or greater than 30 mum. MvO2 increased with 1,000 muM propofol, whereas coronary venous oxygen tension and content remained unchanged. MvO2 decreased with thiopental associated with a significant increase in coronary venous oxygen tension and content. In six buffer-perfused hearts, basal coronary blood flow was much greater and MvO2 less than in blood-perfused hearts. Left ventricular dP/dt(max) and dP/dt(min) decreased with 30, 100, and 300 muM propofol. Propofol vehicle did not change coronary blood flow, myocardial performance, or MvO2 of blood- or buffer-perfused hearts. Conclusions. When compared to a reference drug such as thiopental, propofol did not depress the myocardial performance of blood-perfused rabbit hearts. The type of the perfusate (blood vs. buffer), however, had a major influence on the myocardial effects of propofol.