The metabolic disposition and pharmacokinetics of acyclovir have been studied as part of the clinical evaluation of the drug in humans. Data from 10 studies have been summarized and, when appropriate, pooled across studies for further analysis. The principal findings are as follows: Renal excretion is the major route of elimination of acyclovir and is dependent, in part, on active tubular secretion. Total body clearance (Cltot) and half-life are dependent on renal function as evaluated by estimated creatinine clearance (Clcr). Cltot is markedly reduced in the anuric patient. Plasma protein binding is low and drug interactions involving binding displacement are not anticipated. Acyclovir levels in cerebrospinal fluid are approximately 50 percent of corresponding plasma levels. Dose-independent pharmacokinetics is observed in the range of 0.5 to 15 mg/kg. Proportionality between dose and plasma levels is seen after single doses or at steady state after multiple dosing. Similar plasma levels are achieved in adults and pediatric patients (greater than 1 year) when equivalent doses are given based on body surface area. Intrasubject variability of acyclovir disposition is low. Much but not all intersubject variability in Cltot can be explained by differences in renal function. Dosage adjustment for various stages of renal impairment are proposed based on the observed relationship between Cltot and Clcr.