The therapeutic options for interfering with the electrical instability of a pathologically remodeled or ischaemic heart remain limited. Of increasing importance become interventions which target the fatty acid composition of blood and membrane lipids. In particular, the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide parameters for stratification of risks associated with severe arrhythmia disorders and sudden cardiac death. Since EPA and DHA appear to have their anti-arrhythmogenic actions when present as free fatty acids, the parameters which determine a critical free fatty acid concentration are of great interest. In the present study, conclusions on EPA and DHA incorporation in blood lipids are derived from the administration of Omacor which contains highly purified (84%) EPA and DHA ethyl esters and reduced the risk of sudden cardiac death by 45% in post-myocardial infarction patients (GISSI-Prevention study). The "EPA+DHA level" is described as risk identifying parameter for severe arrhythmia disorders, particularly if they are associated with myocardial ischaemia. It appears essential not only to build up body stores for release of EPA and DHA but to provide also a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to more rapidly absorbed triacylglycerols from fish, ethyl esters are taken up slowly within 24 h. For the administration of 1 g/day Omacor to healthy volunteers, it is shown that in whole blood EPA is increased from 0.6% to 1.4% within 10 days while DHA is increased from 2.9% to 4.3%. After withdrawal, the EPA and DHA levels approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 30 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for severe arrhythmia disorders and sudden cardiac death. The administration of 840 mg/day of EPA and DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with protection from sudden cardiac death. The pharmacological effects of ethyl esters are compared with the naturally occurring EPA and DHA triacylglycerols present in fish or fish oils which are of interest in primary prevention of cardiovascular disorders.