Fish oil amplifies the effect of propranolol in mild essential hypertension. Forty-seven male patients with mild essential hypertension were randomly allocated to three subgroups. After a run-in period of 4 weeks, the first subgroup (n = 16) received propranolol (80 mg/day) for 36 weeks followed by a placebo period of 4 weeks. The second subgroup (n = 15), after a run-in period of 4 weeks, was given a supplement of encapsulated fish oil (9 g/day) for 36 weeks with a subsequent period of 4 weeks in which fish oil placebo was given. The third subgroup (n = 16), after a run-in period of 4 weeks, was given propranolol (80 mg/day) for 12 weeks, propranolol (80 mg/day) plus fish oil capsules (9 g/day equivalent to 1.8 g/day of eicosapentaenoic acid and 1.1 g/day of docosahexaenoic acid) for 12 weeks, propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent period of 4 weeks when propranolol placebo was administered. The results indicate a blood pressure-lowering effect of fish oil, which was comparable with that of propranolol. The simultaneous intake of fish oil plus propranolol was more effective than propranolol or fish oil alone. Propranolol treatment resulted in a decrease of plasma norepinephrine, plasma renin activity, and thromboxane B2 formation. After fish oil supplementation, plasma norepinephrine and thromboxane B2 formation were likewise reduced, whereas plasma renin activity appeared increased. The decrease of serum triglycerides, total and low density lipoprotein cholesterol as well as the rise of high density lipoprotein cholesterol are concomitant beneficial effects, which justify the consideration of fish oil alone or in combination with antihypertensive drugs for the treatment of mild hypertension. 