The effect of 10 minutes of occlusion, and release of occlusion, of the left anterior descending coronary artery on vulnerability to ventricular fibrillation was studied in 15 dogs. Ventricular fibrillation threshold was determined by inducing a sequence of three closely coupled extrasystoles (sequential R/T pulsing). Within 3 minutes of occlusion the current required to induce fibrillation decreased from a control value of 56 +/- 7 ma (mean +/- standard error) to 1.6 +/- 0.3 ma (P less than 0.001). It remained at this level for about 4 minutes and then rapidly returned to the control level in 8 of 10 dogs. Upon release of occlusion at 10 minutes, the ventricular fibrillation threshold was again greatly reduced; this period of reduction occurred shortly after reperfusion and was of brief duration. After both occlusion and release the duration of the ventricular vulnerable period was prolonged. The time course of change in cardiac vulnerability parallels the altered susceptibility to ventricular fibrillation after coronary arterial occlusion and release. These results recommend sequential R/T pulsing as a useful technique for probing changes in cardiac vulnerability under diverse experimental conditions.