In experimental models preconditioning by brief ischemic episodes protects myocardium from ventricular arrhythmias (VA) during a subsequent coronary occlusion. Aim of the present study was to evaluate whether in man protection from ischemia-induced arrhythmias may occur following spontaneous ischemic episodes. We analyzed episodes of ST elevation (ST↑) found during Holter recordings in 9 patients (pts, 8 men, age 60 +/- 8 yrs) with variant angina who frequently developed VA (i.e. < 5 premature ventricular beats/min. and/or runs of ventricular tachycardia) during ST↑. For each ischemic episode we determined the severity and duration of ST↑, the occurrence of VA and the interval from the previous episode of ST↑. A total of 118 episodes (20 associated with VA) were recorded. The interval between each ischemic episode with VA and the previous one (192 +/- 286 min) was longer than that of episodes without VA (67 +/- 86 min, p < 0.05). VA were found in 5% of ST↑ episodes (n = 58) occurring within 30 min from the previous one and in 28% of ST↑ episodes (n = 60) not preceded by ST↑ in the previous 30 min (p < 0.01). Finally, we analyzed 12 clusters of ischemic episodes occurring in periods of 30 min and showing VA in at least one episode. The number of premature ventricular beats per min was strikingly higher during the first episode compared with the last one (27 +/- 9 vs 2.7 +/- 3.6, p < 0.01); the first and the last episode of the clusters did not differ in severity (1.9 +/- 0.9 vs 2.0 +/- 1.6 mm) and duration of ST↑ (4.0 +/- 3.8 vs 6.5 +/- 13 min). Thus, our data indicate that transient ischemia confers a significant protection from ischemia-induced VA in pts with variant angina, unrelated to a reduction in severity or duration of ischemia.