High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol (TG), which may contribute to the positive impact of these fatty acids on the risk of CVD. The present study aimed to establish the differential impact of EPA and docosahexaenoic (DHA) on plasma lipids and apo in adults. Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study, receiving an EPA-rich oil (4·8 g EPA/d), DHA-rich oil (4·9 g DHA/d) or olive oil as control, for a period of 4 weeks. No effects of treatment on total cholesterol, LDL-cholesterol or HDL-cholesterol were evident. There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment (P¼ 0·032), with the 15 % decrease in the EPA group failing to reach significance (P¼ 0·258). There were no significant inter-group differences in response to treatment for plasma apoA1, -C3 or -E levels, although a significant 15 % within-group increase in apoE was evident in the EPA (P¼ 0·006) and DHA (P¼0·003) groups. In addition, a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group, suggesting a positive impact of DHA on HDL particle size. The DHA intervention resulted in a significant increase in the proportion of EPA P¼0·000 and DHA P¼0·000 in plasma phospholipids, whilst significant increases in EPA P¼0·000 and docosapentaenoic acid P¼ 0·002, but not DHA P¼0·193, were evident following EPA supplementation (P, 0·05). Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile.