42K exchange was studied before and after total ischemia in isolated, blood-perfused rabbit interventricular septa at 37 degrees C and 72 beats/min. Of 11 septa made ischemic for up to 45 min after 42K labeling to asymptotic values, 10 showed no decline in 42K as measured by tissue probe counts 5 min after reperfusion. Of these 10 septa, 7 showed a 1.4-14.2% increase in 42K counts on reperfusion. Three of four muscles reperfused after 60 min of ischemia showed progressive 42K losses. Of 14 septa previously labeled with 42K, 9 showed a parallel decrease in 42K-exchange rate constants as measured by tissue probe and effluent during washing out after 2-45 min of ischemia. In five other muscles a nonparallel decrease in rate constants as measured by tissue probe and effluent during washout indicated inhomogeneity of 45K exchange. These results indicated no persistent impairment in Na pump activity for 30-45 min of total ischemia. After ischemia for 45 min or less there was no consistent relationship between recovery of mechanical function and preservation of 42K content. After 60 min of ischemia, irreversible mechanical injury was associated with loss of tissue potassium.