OBJECTIVE The purpose of this study was to evaluate the interaction of a linoleic acid enriched diet with NaCl on the development of hypertension in Dahl salt sensitive (Dahl-S) rats and in two-kidney, one-clip Sprague Dawley rats. METHODS In both experimental models, separate groups of animals were fed either linoleic acid enriched (provided as safflower oil) or control (containing coconut oil) diets for 5 weeks. Diets were further subdivided on the basis of either a low NaCl (0.3%) or a high NaCl (3.0%) content. Tail systolic blood pressure, direct mean intra-arterial pressure, and cardiac output were measured in chronically instrumented, conscious rats. RESULTS In Dahl-S, on both NaCl intakes, and in two-kidney, one-clip rats on a high NaCl diet, safflower oil had no effect on arterial pressure. In contrast, in two-kidney, one-clip rats fed the low NaCl diet, both indirect tail systolic blood pressures and direct mean arterial pressure were lower (p<0.01) in animals on the linoleic acid enriched diet; total peripheral resistance was also decreased (p<0.01). CONCLUSIONS Safflower oil has a hypotensive effect only in the two-kidney, one-clip rat on a low NaCl, but not on a high NaCl intake, and not in Dahl-S rats. Additional studies are required to identify the mechanism(s) for the hypotensive effect of safflower oil and to define the relationship of this animal study to human hypertension.