This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids In the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before and at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artlfactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 hours, respectively. At 8 minutes, lysophospholipid levels in ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in tbe ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia gtudied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophoapholiplds levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate elcctrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enrymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.