The effect of regional myocardial ischemia complicated by ventricular fibrillation (VF) on the ultrastructure of subendocardial (SE) and false tendon (FT) Purkinje cells (PC) was studied in anesthetized dogs. In all cases of early ischemia with spontaneous VF, many PC exhibited ultrastructural damage as early as 2 min after the onset of ischemia. The changes noted were: intercalated disk dissociation, sarcoplasmic reticulum vacuolization (SRV), supercontraction, mitochondrial swelling, and sarcolemmal defects (rigor cells). The appearance of at least some rigor PC seemed to precede spontaneous VF, since these cells were absent from the conduction systems in control hearts in which VF was induced by electric shock or reperfusion, from hearts from sham-operated dogs, or from hearts subjected to longer periods of uncomplicated myocardial infarction. These observations indicate that alterations in SE and FTPC may play a role in the pathogenesis of sudden death due to early myocardial ischemia. The mechanism of this rapid damage of PC remains obscure.