In previous studies in rats given mercuric chloride (HgCl2), administration of furosemide has been found to either attenuate, exacerbate, or not affect the severity of the acute renal failure (ARF) otherwise expected to obtain. In the current study in rats given large doses of furosemide and in which urinary fluid losses were replaced by intravenous infusions of saline, administration of HgCl2 induced less severe ARF than that induced in rats not given furosemide and saline infusions. In rats not given furosemide, a diuresis induced by continuous reinfusion of urine also conferred protection against the nephrotoxic effect of HgCl2. These findings suggest that in rats given HgCl2: diuresis per se is the critical determinant of any salutary effect of furosemide and the protective effect of diuresis does not depend on renal elimination of mercury.