This evidence report is one of three prepared by the Tufts-New England Medical Center Evidence-based Practice Center (EPC) concerning the health benefits of omega-3 fatty acids on cardiovascular diseases. The aim of these reports is to summarize the current evidence of the health effects of omega-3 fatty acids on: cardiovascular diseases, cancer, child and maternal health, eye health, gastrointestinal/renal diseases, asthma, autoimmune diseases, immune-mediated diseases, transplantation, mental health, and neurological diseases and conditions. The focus of this report is on arrhythmogenic mechanisms in animal and isolated organ and cell culture studies. Arrhythmias are thought to be the cause of "sudden death" in heart disease. Animal studies have suggested that omega-3 long-chain polyunsaturated fatty acids (LC PUFAs), such as eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), engage in multiple cytoprotective activities that may contribute to antiarrhythmic mechanisms. In this report, we examine evidence that omega-3 fatty acids affect cell organelles-such as cardiac ion channels, pumps, or exchange mechanisms-that are involved in cardiac electrophysiology or electrogenesis. The key questions addressed by this report are: 1) What is the evidence from whole animal studies that omega-3 fatty acids affect arrhythmogenic outcomes (and intermediate outcomes)? 2) What is the evidence from cell culture and tissue studies (including animal and human cardiac tissue) that omega-3 fatty acids directly affect cell organelles such as cardiac ion channels, pumps, or exchange mechanisms involved in electrogenesis? In whole animal studies examined for this report, omega-3 fatty acids were fed to whole, intact animals as part of their diet or were infused intravenously. Outcomes examined by these studies include induced arrhythmia, ventricular ectopic beats, and ventricular and atrial fibrillation. In whole animal isolated organ and cell studies, omega-3 fatty acids were fed to whole, intact animals as part of their diet, and organs or cell tissues were subsequently excised from the animal to study outcomes such as arrhythmia, and myocyte contraction and beating rate. In "pure" isolated organ and cell studies, omega-3 fatty acids were applied directly to mammalian tissues or cultured cell lines or incorporated into the membrane of the mammalian tissues or cultured cell lines. Outcomes examined in these studies include induced arrhythmia, myocyte contraction and beating rate, and any other arrhythmogenic outcomes. In examining studies for this report, we focused on several potential arrhythmogenic mechanisms, including contractile parameters, basoelectromechanical parameters, ion pumps, ion channels, and membrane currents.