Captopril (C) causes ARF in hypertensive patients with renal artery stenosis (RAS) with a single functioning kidney (SK). Retrospective studies in two patients showed that episodes of C-induced ARF were preceded by a rise in urinary Na+excretion and a rapid decrease in body weight. These observations prompted us to investigate whether extracellular fluid volume depletion secondary to C-induced natriuresis can be responsible for ARF. Prospective studies were performed in four patients with RAS-SK treated with C. These studies have shown that: (a) ARF is associated with negative Na+balance and is corrected by salt replacement, even without interrupting C; (b) ARF is preceded by a rise in urinary prostaglandin (PG) E2and 6-keto-Flα; (c) ARF is prevented by either saline infusion or aspirin administration; (d) ARF does not occur when the dose of C is not sufficient to raise PGs and urinary Na+excretion. We conclude therefore that C-induced ARF in patients with RAS-SK can be secondary to salt depletion dependent on a raised secretion of PGs.