We report two cases of herpes-zoster in which the administration of acyclovir to patients with end-stage renal failure treated by continuous ambulatory peritoneal dialysis (CAPD) resulted in acyclovir neurotoxicity, even though the doses administered were within those recommended by the manufacturer's data sheet for patients with renal failure. Acyclovir removal was negligible with peritoneal dialysis and one patient died. The other patient was successfully treated with hemodialysis, which effectively reduced plasma concentrations, resulting in an improvement in conscious state. Acyclovir neurotoxicity should be considered in patients with renal failure who have been treated for viral infections, in whom the conscious state has deteriorated despite normal brain computed tomography (CT) scan and lumbar puncture investigations. Hemodialysis is the preferred treatment for the rapid removal of acyclovir.