Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl Salt-Sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T lymphocytes isolated from the kidney in comparison to circulating T lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n=13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11 day period of high salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug-treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared to control SS. Moreover, the increase in MAP following 11 days of high NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138±3 vs. 149±3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n=8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs the control group. The total number of T and B lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney.