Ribavirin is a synthetic guanosine analog with activity against DNA and RNA viruses. It was studied in human trials, and no marked adverse effect was reported beyond the potential for teratogenicity and reversible mild anemia. An 8-year-old girl received a multivisceral transplant and developed adenoviral pneumonia. She was treated with intravenous ribavirin and became hyperammonemic. Discontinuation of ribavirin led to a decrease in ammonia levels. This pattern was repeated when the drug was restarted and discontinued. We hypothesize that in a toxic environment the interaction of ribavirin with hepatocellular mitochondrial enzymes may lead to hyperammonemia.