This study was undertaken to examine the effects of lidocaine (L) (400 mg/liter) in a normokalemic crystalloid (S) (K+: 5 meq/liter, Na+: 120 meq/liter) and in a hyperkalemic crystalloid cardioplegic solution (K) (K+: 25 meq/liter, Na+: 120 meq/liter) during 90 min of hypothermic (28°C) aortic occlusion followed by 45 min of reperfusion (R). Four groups of dogs were studied: group I (S), n = 6; group 2 (S + L), n = 6; group 3 (K), n = 6; group 4 (K + L), n = 6. Left ventricular (LV) function was defined as percentage changes in center of mass between pre- and postarrest function curves. Regional myocardial flow was measured with 9 μ radioactive microspheres and myocardial metabolism monitored by lactate and oxygen utilization. Ventricular biopsies were obtained for measurement of myocardial ATP, creatine phosphate, and water content. Percent recovery of LV function curves at the end of (R) was 59.2 ± 3.9% in group 1, 85.0 ± 4.3% in group 2, 71.5 ± 4.9% in group 3, and 87.0 ± 4.5 in group 4 (group 1 vs group 2, P < 0.01; group 3 vs group 4, P < 0.05). Metabolic recovery was evaluated at 5, 20, and 45 min of (R). Only group 3 (K) demonstrated persistent lactate production at 5 min of (R) ( P < 0.01). The hyperkalemic groups failed to return to control levels of oxygen utilization after 5 min of (R) (group 3, P < 0.05; group 4, P < 0.05). LV endocardial/epicardial myocardial blood flow ratio demonstrated greater increase in hyperkalemic groups (group 3, P < 0.01; group 4, P < 0.01) at 5 min of (R). ATP was significantly decreased in groups 1, 3 and 4, but not in group 2 at the end of ischemia (group 1, P < 0.01; group 3, P < 0.01; group 4, P < 0.05) and after 45 min of (R) (group 1, P < 0.05; group 3, P < 0.01; group 4, P < 0.01). These results demonstrate that lidocaine has a myocardial protective effect which is superior to standard hyperkalemic cardioplegia. Moreover, lidocaine has an additive salutary effect during potassium cardioplegia. Persistent metabolic derangements post reflow in the hyperkalemic groups suggest deleterious effects of hyperkalemia on subendocardial protection.