"Ischemic" blood was obtained in pigs from a local coronary vein on release of coronary artery occlusion. The effects of this blood on transmembrane potentials of muscle strips taken from the same heart were compared with control blood. Whereas action potentials remained stable in control blood, ischemic blood collected after more than 15 minutes of coronary occlusion produced shortening of action potential duration, reduction of resting potential, upstroke velocity and amplitude, then postrepolarization refractoriness and finally unresponsiveness. Ischemic blood collected after shorter periods of coronary occlusion produced only mild effects (shortening of action potential and postrepolarization refractoriness). These effects of ischemic blood could not be attributed to increased potassium concentration even in combination with acidosis, hypoxia and hypoglycemia. It appears that during ischemia unidentified factors are released which have potent depressant effects on the excitability of even normal myocardium.