Changes in myocardial K+ handling were examined during ventricular fibrillation and subsequent CPR in ten domestic swine. During ventricular fibrillation, there was initial K+ efflux from the myocardium which was followed by myocardial K+ uptake during precordial compression. After successful defibrillation, a washout in K+ was observed. Coronary potassium clearance was inversely related to the myocardial [H+], PCO2, and lactate production. A negative correlation between cardiac vein [K+] and myocardial [H+] was observed (r = .88), supporting the concept that H+ extrusion is associated with K+ uptake of myocardial cells. Normal conditions were re-established within 60 min after restoration of spontaneous circulation. The myocardial uptake of K+ during CPR contrasted with increased K+ efflux from other tissues such that there were net increases in the K+ content of arterial and mixed venous blood. The implications of such myocardial K+ uptake during CPR on resuscitability is the subject of continuing study.