We report 5 cases of acute reversible renal failure coinciding with the onset of treatment with captopril in patients with severe drug-resistant hypertension. There was no clinical or laboratory evidence for an immunologic or toxic insult, although in 1 patient we found a transient leukocyturia and mild proteinuria. A mere hypoperfusion of the kidney does not seem sufficient to account for all 5 observations: in 3 of them changes in blood pressure did not parallel changes in renal function. We propose that, in addition to hypoperfusion, captopril alters renal function by an additional intrarenal hemodynamic effect. The 5 patients had severe renovascular disease which might thus represent a significant risk factor in the development of captopril-induced acute renal failure.