Silver sulfadiazine (SSD) cream is a potent agent for the treatment of burns. In a patient with end-stage renal disease, we observed a marked elevation in serum silver concentration in the course of 2 weeks of SSD cream therapy (200 g/d). Serum concentration of silver reached a maximum of 291 ng/mL in association with a rapid deterioration of mental status. SSD therapy was discontinued, and hemodialysis, hemofiltration, or plasma exchange was continually performed. Four months later, the patient died. At autopsy, profoundly elevated levels of silver were found in brain tissues of this patient (617.3, 823.7 ng/g wet tissue weight in the cerebrum and cerebellum, respectively). To determine the most efficient therapy to remove silver from serum, we compared hemodialysis (HD), hemofiltration (HF), and plasma exchange (PE). Both plasma exchange and hemofiltration were effective in decreasing serum silver, and their effects were additive. By contrast, HD was ineffective in reducing serum silver. This case illustrates that, on SSD cream therapy, burn patients with disturbed renal function are at risk of accumulating silver in serum and tissue to the level that may cause neuralgic decompensation. Removal of serum silver can best be effected by PE, particularly when combined with HF. In contrast, HD per se does not appear efficacious. None of these blood purification modalities improves deterioration of neurological status potentially attributable to silver deposition in brain tissues.