(n-3) Fatty acids may reduce the risk of sudden death by preventing life-threatening cardiac arrhythmia. A standard electrocardiogram (ECG) may be used to detect clues as to the mechanism by which (n-3) fatty acids affect the electrophysiology of the heart. An earlier study showed that (n-3) fatty acids decreased the duration of the heart-rate corrected QT interval (QTc) in dogs. However, effects of (n-3) fatty acids on the standard ECG of humans have not been reported. Therefore, we investigated the effect of (n-3) fatty acids on QTc, QRS duration, apex-to-end-T duration, T-loop morphology and spatial QRS-T angle in apparently healthy men and women aged 50 to 70 y. Subjects (n = 42/group) received either capsules providing 1.5 g (n-3) fatty acids daily or placebo for 12 wk. ECG were recorded before and after intervention. None of the ECG characteristics were affected by (n-3) fatty acids. The QTc decreased by 0.8 ms or 0.2% (95% confidence interval, -6.1 to 4.4 ms) in subjects that consumed (n-3) fatty acids compared with the placebo group. These results do not support the hypothesis that (n-3) fatty acids prevent arrhythmia through electrophysiologic effects on heart cell membranes. However, an effect on the ECG in more susceptible populations can not be excluded.