The l-valyl ester of acyclovir is generally well tolerated. Elderly patients and those with chronic renal failure are most susceptible to adverse effects involving the central nervous system. Renal failure associated with neurotoxicity following valacyclovir is generally reported among patients with preexisting impaired renal function [1, 2, 3, 4]. A 62-year-old, 65-kg, posttraumatic paraplegic woman with limited upper limb movement and bladder dysfunction complained of chest pain followed by thoracic vesicular rashes. Her general practitioner prescribed valacyclovir 1 g three times a day. Apart from her disability she was healthy and her past medical history was unremarkable. Four days later the patient was admitted to the general medical ward because of progressive altered mentation, with a Glasgow Coma Scale of 10 (E2 V3 M5). She was stuporous and oliguric but heart rate, arterial pressure, temperature, and arterial blood gases were normal. Common laboratory tests were also normal except for urea nitrogen at 56 mg/dl (normal 10–50 mg/dl) and creatinine at 1.8 mg/dl (normal 0.6–1.1 mg/dl). Valacyclovir therapy was maintained. Neither cerebral computed tomography, without contrast medium, nor abdominal ultrasound examination revealed any abnormalities. The next day urea nitrogen was 71 mg/dl, creatinine 2.6 mg/dl, and her neurological condition further worsened (E2 V1 M3), but a encephalic computed tomography without radiocontrast was again negative. She was therefore admitted to our ICU, intubated, and mechanically ventilated. Electroencephalography showed a nonconvulsive epileptic status, and phosphenytoin treatment was started. A lumbar puncture was performed to rule out meningoencephalitis, but no microorganisms were seen on a Gram stain. Cultures of cerebrospinal fluid, blood, and urine were also negative. Diuresis during the first 24 h was 3.8 l, and she remained polyuric throughout her ICU stay. Antiviral therapy was finally stopped. Twenty-four hours after discontinuation of valacyclovir there was a rapid improvement in renal function and her Glasgow Coma Scale rose to 9 (E3 Vt M5). The patient was extubated 2 days later with full neurological recovery and was discharged from the ICU, with creatinine concentration of 0.7 mg/dl and nitrogen of 17 mg/dl. The altered mentation, confusion and coma in our case aere consistent with the typical findings of acyclovir neurotoxicity [5]. The absence of fever, focal neurological deficits, and signs of lateralization on electroencephalography, along with normal results of cerebrospinal fluid analysis and cerebral computed tomography, generally aid in ruling out viral encephalitis. Unfortunately a baseline serum creatinine concentration was not obtained in our patient before hospital admission, but the temporal relationship between the initiation of valacyclovir and the onset of adverse effects strongly implicate valacyclovir as the cause of patient’s worsening and suggests that acute renal failure and coma can occur early. Furthermore, 4 days after ICU admission serum creatinine concentration and nitrogen were normal (0.7 and 17 mg/dl). Due to fear of herpes zoster encephalitis valacyclovir administration was maintained without dose adjustments despite the progressive impairment of renal function in presence of a brisk, but deceptive, urinary flow. In conclusion, valacyclovir can also impair renal function in elderly patients without preexisting renal failure and, without appropriate dose reduction, can induce life-threatening neurotoxicity.