Acetazolamide, furosemide, chlorothiazide and amiloride are pharmacologic agents that act in the proximal tubule, loop of Henle, early distal tubule and late distal tubule, respectively. These diuretic agents were used to evaluate the functional integrity of discrete segments of the nephron in the neonatal rat following treatment with a known nephrotoxicant. Six-day old rats were treated s.c. with the proximal tubule toxicant mercuric chloride (1, or 3.16 mg/kg) or saline. Twenty-four hr later, when evidence of mercury nephrotoxicity is detectable, creatinine clearance (CCr) and the fractional excretion (FE) of water and various components of the filtrate were determined during a 2 hr clearance period immediately following injection of a diuretic. The effects of mercury (3.2 mg/kg) were consistent with its ability to cause acute renal failure and proximal tubular necrosis and also indicated an apparent disruption of the cycling of urea in the nephron. A decrease in the FE of water, combined sodium and potassium, and total osmotic solutes indicated that the diuretic response to acetazolamide was markedly attenuated in the mercuric chloride treated pups whereas the responses to furosemide, chlorothiazide and amiloride were not altered by mercury treatment.