Abstract--Hypertension is accompanied by systemic oxidative stress, inflammation, and priming of peripheral polymorphonuclear leukocytes (PMNLs), yet the involvement of these factors in the pathophysiology of hypertension is incompletely understood. We investigated the relationship between oxidative stress, primed PMNLs, and inflammation and the development of hypertension in the Sabra rat model of salt-sensitive hypertension. Sabra hypertension-resistant rats (SBN/y) (salt-resistant) and Sabra hypertension-prone rats (SBH/y) (salt-sensitive) were studied under normal conditions or during salt loading. Systolic blood pressure (BP) was measured by the tail-cuff method. The extent of oxidative stress was evaluated by the rate of superoxide release from PMNLs, plasma-reduced glutathione (GSH) levels, malondialdehyde (MDA) levels (estimated by thiobarbituric acid-reacting substances), and plasma-carbonylated fibrinogen (Western blotting). Plasma fibrinogen levels and the peripheral PMNL count served as indices of inflammation. In SBH/y and SBN/y provided regular chow without salt loading, BP did not rise above baseline values, yet superoxide release, plasma MDA, carbonylated fibrinogen, and PMNL count were higher in SBH/y than in SBN/y, whereas GSH levels were lower in SBH/y. Four weeks of salt loading resulted in a gradual increase in systolic BP in SBH/y to 205±3 mm Hg, whereas BP remained in SBN/y at baseline normotensive levels. All the parameters reflecting oxidative stress and inflammation were further aggravated with the development of hypertension in salt-loaded SBH/y. We conclude that primed PMNLs, oxidative stress, and inflammation antecede the development of hypertension in this experimental model of hypertension.