The contribution of elevated aldosterone to the pathogenesis of malignant, Ang II-dependent hypertension remains uncertain. Therefore, we examined if chronic mineralocorticoid receptor (MR) blockade attenuates the development of malignant hypertension in transgenic rats with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Systolic blood pressure (SBP) was measured by radiotelemetry in male TGR rats in 3 groups: 1) Control (n=9), Hypertensives (HT; n=8), and 3) Hypertensives + spironolactone (11 mg/kg/d sc; HTS; n=8). Malignant hypertension was induced with dietary indole-3-carbinol (0.3%) for 10 days. Metabolic measurements were taken at the beginning of the study and at days 2 and 9. HT exhibited elevated SBP (125±3 vs 187±5 mmHg), plasma renin activity (PRA; 5±1 vs 29±10 ng Ang I/ml/hr), plasma Ang II (175±39 vs 611±74 fmol/ml), and plasma aldosterone (110±14 vs 1954±366 pg/ml). Urinary aldosterone excretion (U_aldoV) increased 5.5-fold by day 2 and an additional 90% by day 9. HT was associated with a 1.8-fold increase in proteinuria by day 9 that was alleviated by treatment with spironolactone (25±5 vs 13±3 mg/d) suggesting that aldosterone contributes to the renal damage observed in malignant hypertension. Urinary Na⁺ excretion (U_NaV) was decreased 76% on day 2 despite a 6-fold increase in U_aldoV. Decrease in U_NaV on day 2 in HT suggests that increased aldosterone increased Na⁺ reabsorption; however the lack of a change in SBP between HT and HTS suggests that mechanisms independent of aldosterone stimulation make a greater contribution to the maintenance of elevated arterial pressure in malignant hypertension in Cyp1a1-Ren2 transgenic rats.