The main goal of this project was to study the effect of amiodarone upon ventricular fibrillation and defibrillation thresholds (VFT and VDT) in the canine heart under normal and ischemic conditions. Both parameters were assessed in 11 dogs, each experiment consisting of three consecutive phases: (a) control, which resulted in VFT = 27.9 (S.D. = 15.5) and VDT = 43.9 (S.D. = 4.5); (b) drug, with VFT = 63.5 (S.D. = 32.8) and VDT = 57.8 (S.D. = 11.3), and (c) coronary occlusion, with VFT = 44.7 (S.D. = 21.6) and VDT = 57.1 (S.D. = 11.0). These values are overall means scaled to ventricular weight (microA/g for VFT and mA/g for VDT). Both VFT and VDT in (b) and (c) were, on the average, greater than in (a) and these differences were statistically significant (P less than 0.01, paired t-test). The animals were kept normothermic (37.3 degrees C, S.D. = 0.6) within normal values for the acid-base state. We concluded that amiodarone increased the VFT significantly. Similarly, it increased VDT. However, although the latter change was statistically significant, we believe it would not be important from a physiological or clinical point of view.