This study was conducted to compare the effects of omega3 fatty acids, taken as fish or fish-oil supplements in the setting of a high- or low-fat dietary background, on blood pressure and heart rate in men with moderate cardiovascular risks. One hundred twenty men were randomly allocated to five high-fat (40% of daily energy) and two low-fat (30% of energy) groups to undertake a 12-week dietary intervention period involving fish, fish oil, or a combination of these. Sodium intake was restricted to less than 90 mmol/d. The five high-fat groups were assigned to take either 6 or 12 fish-oil capsules daily, fish or a combination of fish oil and fish, or placebo capsules. The two low-fat groups took either fish or placebo capsules. Fish meals were devised to provide 1.3 g of eicosapentaenoic acid daily, equivalent to that contained in 6 fish-oil capsules. Subjects were instructed to eat a selection of fish that provided an average of 3.65 g/d (range, 3.2 to 4.1 g/d) of total omega3 fatty acids. Subjects were seen at regular intervals during the baseline and dietary intervention periods for measurement of weight, blood pressure, heart rate, dietary compliance, urinary electrolyte excretion, platelet phospholipid fatty acids, blood glucose, and insulin concentration. There was a greater fall in both systolic and diastolic blood pressures in subjects allocated fish or fish oil, particularly in the low-fat groups, compared with control subjects. However, there was no significant group effect. For all groups combined, there were highly significant relations, independent of changes in weight and urinary sodium and potassium excretions, between the fall in blood pressure and the increase in omega3 and decrease in omega6 fatty acids in platelet phospholipids. The fall in heart rate observed in the fish and fish-oil-supplemented groups was significantly related to the changes in platelet omega3 and omega6 fatty acids. It is proposed that, in addition to previously reported alterations in platelet eicosanoid production, similar changes in fatty acid composition at the vascular and myocardial cellular levels result in the cardiovascular responses observed.