Propylene glycol is a solvent that is used in many oral, injectable, and topical medications. Although uncommon, acute renal failure has been attributed to propylene glycol. The mechanism of propylene glycol-mediated renal injury is unknown. We report a case of acute renal failure in a 16-year-old boy given large doses of pentobarbital and phenobarbital, both of which are solubilized with propylene glycol. A renal biopsy showed proximal renal tubular cell swelling and vacuole formation. The data from this case suggest that the reversible acute renal failure caused by propylene glycol is attributable to proximal renal tubular cell injury.