The potential antihypertensive effects after prolonged use of small doses of fish oils remain undefined. Therefore, we conducted a randomized, double-blind, controlled crossover study comparing low doses of n-3 fatty acid supplementation with n-6 fatty acids on blood pressure in 33 subjects with mild hypertension. After a 6-week stabilization period, subjects ingested either 2.04 g/d of n-3 fatty acids or safflower oil (4.8 g/d of linoleic acid) for 12 weeks, then crossed over to the alternative encapsulated oil for another 12 weeks, after a 4-week washout period. All antihypertensive drug therapy had been discontinued. For the combined data, there were significant reductions from pretreatment values for supine diastolic (-2.4 mm Hg) and sitting systolic (-4.1 mm Hg) blood pressure after fish oil; no significant changes occurred after safflower oil control. Compared with safflower oil, fish oil supplementation was associated with a statistically significant reduction in mean supine diastolic blood pressure of 3.7 mm Hg (95% confidence interval, -7.3 and 0.1). Sitting diastolic and mean arterial pressures showed a sequence effect; therefore, only the initial period was used in an analysis of their responses. There were significant decreases from pretreatment values for sitting diastolic (-4.4 mm Hg), mean arterial (-5.1 mm Hg), and systolic (-6.5 mm Hg) blood pressure after fish oil. The differences between groups after the 12-week period remained statistically significant for sitting diastolic and sitting mean arterial blood pressures. No adverse changes were noted in plasma levels of lipid-related measures.