We have found that indapamide has free radical scavenging properties and stimulates prostacyclin generation in vascular smooth muscle cells. In this study, we investigated whether indapamide exhibits radical scavenging effects in vivo and whether these properties are related to renal protection in Dahl salt-sensitive (Dahl S) rats. Indapamide (4mg/kg body weight per day for 5 weeks) ameliorated the development of hypertension in Dahl S rats fed a high salt (6% NaCl) diet. The blood pressure reduction was associated with a decrease in proteinuria, a decrease in urinary n-acetyl-β-D-glucosaminidase excretion, and an increase in glomerular filtration rate. Moreover, morphological investigation revealed improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injuries, seen in the salt-induced hypertension. These beneficial properties were accompanied by a significant decrease in the capacity for lipid peroxide formation in the renal homogenates. In contrast, trichloromethiazide, which reduced the blood pressure to the same extent as indapamide, did not lower lipid peroxide formation in the kidney or exert protective effects on the renal glomeruli or arteries. Thus, the evidence suggests that the diuretic indapamide exhibits radical scavenging effects on the kidney which may contribute to attenuating the renal injuries seen in salt-induced hypertension in Dahl S rats. (Hypertens Res 1992; 15: 17-26)