The effect of lidocaine on the palmitoyl-L-carnitine (PAL-CAR)-induced mechanical and metabolic derangements was studied in Langendorff rat hearts, perfused aerobically at a constant flow rate and paced electrically. PALCAR (5 µmol/l) increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., mechanical dysfunction), and decreased the tissue levels of adenosine triphosphate and creatine phosphate (i.e., metabolic change). These mechanical and metabolic alterations induced by PALCAR were concentration-dependently attenuated by lidocaine (20, 50 or 100 µmol/l). Nevertheless, lidocaine (20, 50 or 100 µmol/l) did not affect the mechanical function and energy metabolism of the normal (PALCAR-untreated) heart. These results indicate that lidocaine has a cardioprotective action against the PALCAR-induced mechanical and metabolic derangements.