A blunted pressure-natriuretic response characterizes hypertension in the Dahl salt-sensitive rat Long-term L-arginine administration prevents hypertension in these animals. To determine if long-term L-arginine corrects the pressure-natriuretic response, we gave salt-sensitive rats on an 8% sodium diet L-arginine or vehicle daily for 3 weeks. Identically treated salt-resistant rats served as controls. After 3 weeks, acute pressure-natriuresis curves were determined. To control for hypertension-induced renal damage, we also examined pressure natriuresis in salt-sensitive rats after short-term L-arginine. Baseline mean arterial pressure was 158±3 mm Hg in vehicle-treated salt-sensitive rats and 127±3 mm Hg in chronically L-arginine–treated salt-sensitive rats. During alterations in perfusion pressure, renal blood flow was autoregulated in all groups. Glomerular filtration rate was autoregulated in salt-resistant rats and L-arginine–treated salt-sensitive rats but fell with decreasing pressure in vehicle-treated salt-sensitive rats. Sodium excretion was greater (P<.05) in L-arginine–treated than in vehicle-treated salt-sensitive rats and did not differ from salt-resistant rats at 100, 125, and 158 mm Hg. The slope of the pressure-natriuresis relation was greater (P<.05) in chronically L-arginine–treated than in vehicle-treated salt-sensitive rats. L-Arginine had no effect on natriuresis in salt-resistant rats. Thus, long-term L-arginine administration normalizes pressure-natriuretic responses in salt-sensitive rats. The effect is not due to the prevention of renal damage and is specific to the salt-sensitive strain. The mechanism may in part result from improvement in autoregulation of glomerular filtration rate.