In the setting of high salt intake, aldosterone is known to stimulate fibrosis in heart and kidney. TGF-b is important for T cell differentiation, matrix homeostasis and tissue repair. Its expression is elevated in mineralocorticoid-salt hypertension. Our aim was to study the possible role of TGF-b signaling in T-cells on aldosterone/salt-induced renal and cardiac damage. 6-month-old male FVB/N (Wt) and transgenic (Tg) mice, expressing a dominant-negative TGF-b type II receptor in T cells under control of the human CD2 promoter where infused either with aldosterone (0.6 mg/d/g body weight) or vehicle via osmotic minipumps. The animals had free access to 1% NaCl or tap water (vehicle group). Blood pressure was measured via tail cuff. After 28 days, animals where sacrificed and blood, urine, hearts and kidneys were removed and snap frozen. During the experimental period systolic blood pressure did not differ between the groups. After 28 days renal weight/tibia length(TL) was increased in both Aldo/NaCl groups, while heart weight/TL only increased in Wt mice upon Aldo/NaCl treatment. During Aldo/NaCl treatment the expression of several genes, reported to be relevant in Aldo/NaCl-induced renal and cardiac injury increased. In the heart of Wt but not Tg the expression of MCP-1, TNF- and PAI-1 increased. In the kidneys of Wt higher mRNA levels for Fn-1, Col1a1, Col3a1, Col4a1 could be detected upon Aldo/NaCl treatment, while in Tg only Col1a1 and Col4a1 mRNA was elevated. Already under control conditions Fn-1, Col1a1 and MMP-2 mRNA was elevated in Tg animals. Under control conditions the TGF-b mRNA level in the kidney was enhanced in Tg, probably due to a missing negative feedback from T-cells. Taken together, our data indicate that TGF-b contributes to Aldo/NaCl-induced renal and cardiac damage by modulating T-cells, and that in the heart inflammatory gene expression is promoted, while in the kidney matrix homeostasis is changed.