The tetradecythioacetic acid (TTA) is a modified fatty acid known to exhibit pleiotropic effects. Firstly, we compared the effect of TTA on the blood pressure in spontaneously hypertensive rats (SHR) with two-kidney, one-clip(2K1C) hypertensive rats. Secondly, we examined mechanisms involved in the blood pressure reduction. TTA had minor effect on systolic blood pressure (SPB) in young SHR up to 8 weeks of age. In 2K1C we confirmed the blood pressure lowering effect of TTA (SPB:173±4 before vs.138±3 mmHg after TTA, p<0.001). No effect on SPB was seen in WKY controls. Plasma renin activity (PRA) was low in SHR and WKY controls and TTA did not change it. PRA decreased from 22.9 ±1.3 ng.ml^-1.h^-1 to 16.2±2.2 ng.ml^-1.h^-1 (p=0.02) in 2K1C Plasma ANG II concentration declined from 101 ± 3 fmole.ml-1 to 81±5 fmole.ml-1 after TTA treatment (p=0.005). In the clipped kidney, tissue ANG I concentration decreased from 933 ±68 fmole^.g^-1 tissue to 518±60 fmole^.g^-1 tissue (p=0.001), and ANG II decreased from 527±38 fmole.g-1 tissue to 149±21 fmole^.g^-1 tissue (p<0.001) after TTA treatment. In the non-clipped kidney, TTA did not change ANG I and moderastely reduced ANG II levels. The RBF response to injection of ANG II into the non-clipped kidney was blunted compared to controls and normalized with TTA treatment (10±2 % before vs. 20±2 %, p<0.001).The results indicate that TTA downregulate the renin-angiotensin system in high renin animals, but has no effect in low renin models