Abstract: The effects of sinomenine (SIN) on action potential and force of contraction were investigated with glass microelectrode in guinea pig heart muscle. SIN at concentrations above 2.7 μmol/l exhibited a dose-dependent negative inotropic action and prolongation in the 20% and 90% repolarization (APD₂₀ and APD₉₀ and effective refractory period (ERP). SIN (27 μmol/l) decreased the maximal upstroke velocity (max) by 10±6%. The amplitude of action potential was also decreased. In the ventricular muscle pretreated with tetrodotoxin (TTX), SIN (27 μmol/l) decreased the amplitude of action potential and maximal rate of depolarization (MRD), and caused a marked prolongation of its duration. Moreover, the effect of acetylcholine (Ach 30 μmol/l) in shortening the APD of atrium was antagonized by SIN (82 μmol/l). These results indicate that SIN may unspecifically inhibit the current of Na⁺, Ca²⁺ and K⁺.