Global ischemia was induced in isolated blood-perfused rabbit interventricular septa at 37 °C beating at 72 beats/min. Uptake of133BaCl2 (0.85 JIM) or85SrCl2 (0.4 JIM) during perfusion with solutions containing 2.5 mM CaCh was monitored by gamma probe. Since barium is not sequestered by sarcoplasmic reticulum, its uptake was used to monitor sarcolemmal function. The uptake of133BaCl2 increased from 21.1 ± 5.5 to 29.5 ± 8.2 pmol/min (P < 0.05) upon reperfusion after 30 minutes of ischemia and from 13 ± 2.9 to 28.5 ± 5.7 pmol/min (P < 0.05) after 60 minutes of ischemia. There was no change in85Sr uptake until reperfusion after 60 minutes of ischemia when it increased from 8.5 ± 1.8 to 29.3 ± 11.4 pmol/min (P < 0.025). The effects of calcium upon recovery were assessed. Ten septa made ischemic for 60 minutes and reperfused with 1.5 mM CaCh recovered 31.6 ± 9.1% of preischemia developed tension. Ten other septa reperfused with red cell perfusate containing 0.75 mM CaCh for 5 minutes, then exposed to red cell perfusate containing 1.5 mM CaCl2 recovered 67.1 ± 7.5% (P< 0.05) of preischemia developed tension. Improved recovery was shown after 20 minutes of ischemia, 77.4 ± 6.1% vs. 103.4 ± 7.8% (P< 0.025). Five septa reperfused with anoxic Tyrode's solution containing 50 /tM CaCh after 15 minutes and 45 minutes of total ischemia showed no decrease in resting tension despite a progressive rise during ischemia. Resting tension upon reperfusion with red cell perfusate depended strongly upon perfusate calcium concentration. Impaired relaxation during ischemia had calcium-dependent and calcium-independent components. A mild sarcolemmal leak ofl33Ba after 30 minutes progressed to severe disruption after 60 minutes of ischemia. Reperfusion with red cell perfusate containing 0.75 mM CaCU for 5 minutes enhanced recovery. Ischemic injury can be significantly modified by the calcium content of the blood with which the myocardium is reperfused.