Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 ± 1.76 μM, range 8.5 - 17.5 μM) with the half-life calculated to be 20.2 ± 4.6 h. Mean plasma levels of 6.29 ± 0.94 μM were within the quoted range to inhibit herpes tester virus (4-8 μM) at 18 h. Haemodialysis (4-5 h) eliminated 51 ± 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 ± 0.8 μM A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 ± 1.0 μM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.