Short-term intervention studies have shown that diets rich in polyunsaturated fats have hypotensive properties. We have studied the long-term effects of dietary fat on blood pressure (BP) using adipose-tissue, fatty acid composition analysis in 399 free-living male subjects (average age, 47 yr). Stepwise-regression analysis showed that adipose linoleic acid (18:2 n-6) was not associated with BP, whereas an absolute 1% increase in linolenic acid (18:3 n-3) was associated with a decrease of 5 mm Hg in the systolic, diastolic, and composite mean arterial BP. Linolenic acid (18:3) comprised only one-eighth the amount of linoleic acid (18:2)--the major polyunsaturate in adipose tissue and hence in the diet (2% vs 16%)--and yet it had a disproportionate association with BP. This may be related to its role as a precursor for the production of prostaglandins and/or other vasoregulators. Dietary manipulation with n-3 fatty acids may be helpful in the treatment and prevention of hypertension.