Purpose. A rare adverse effect observed after dose escalation of topiramate therapy is discussed. A review of published cases, monitoring recommendations, and important counseling information for patients who are prescribed topiramate are described. Summary. A 37-year-old man hospitalized for mental status changes and possible seizure developed hyperchloremic, normal anion-gap, metabolic acidosis. His medical history was significant for AIDS, progressive multifocal leukoencephalopathy, a cerebrovascular accident, a seizure disorder for the past three years, and a pulmonary embolism five months before being admitted to the hospital. The patient was also taking topiramate for two months before being hospitalized for his seizure disorder. His dosage was increased after admission, but no changes were made to his other medications. The only new medication initiated was cefotaxime for 14 days to treat pneumonia. During the following 8 days, the patient continued to receive increased dosages of topiramate. His serum chloride concentration increased daily and his serum bicarbonate decreased. Topiramate was identified as the cause and was discontinued the next day. Six other cases of metabolic acidosis in adults are reviewed, as well as risk factors for metabolic acidosis. Conclusion. After receiving increased dosages of topiramate, a 37-year-old man developed hyperchloremic, normal anion-gap, metabolic acidosis, which resolved after discontinuation of the drug.