Omega-3 fatty acid supplements have been reported to have hypotensive properties in humans, and it has been suggested that this effect is due to altered prostaglandin synthesis. However, such effects are inconsistently found, and interpretation of the literature is confounded by problems with study design. Epidemiologic data are often quoted as showing lower blood pressure in populations that eat large amounts of fish, but this effect also is less clear from the primary data. This review presents population studies of the relationship between consumption of omega-3 fatty acids and blood pressure, problems involved in studying blood pressure, and the studies of lowering blood pressure and vascular reactivity with omega-3 supplements in volunteers. Data on omega-3 fatty acids and endogenous production of prostaglandins are also summarized, with interpretation of investigations of dietary omega-3 fatty acids and vascular control. Recent work addressing a number of controversial points is presented, with the conclusion that pharmacologic doses of omega-3 fatty acids can lower blood pressure in humans but probably do not do so directly via altered production of prostaglandins.