Hyperammonemia is a rare and serious complication of intensive cytotoxic chemotherapy. We report the case of a patient who developed profound idiopathic hyperammonemia following bone marrow transplantation for chronic myelogenous leukemia. Despite rapid institution of hemodialysis, sodium benzoate, and the experimental agent sodium phenylacetate, the patient ultimately succumbed to complications of this metabolic derangement. The literature is reviewed, and recommendations for an approach to this complication of marrow transplantation are proposed.