The pharmacokinetics of intravenously administered acyclovir were studied in 10 patients with advanced malignancies. After doses of 0.5 and 1.0 mg/kg, the slow disposition half-life values (t1/2p) ranged from 2.2 to 3.1 h for the 1-h infusions and from 1.8 to 3.7 h for the 6-h infusions. Plasma levels, measured by radioimmunoassay, reached a maximum at the end of the 1-h infusions and approached steady state at 3 to 4 h into the 6-h infusions. Mean peak plasma concentrations obtained at 0.5 and 1.0 mg/kg administered over 1 h were 3.03 and 5.99 MM, respectively. Mean peak levels for the 6-h infusions were 1.07 MM at 0.5 mg/kg and 2.58 ,uM at 1.0 mg/kg. The mean urinary elimination of acyclovir was 44.7% of the administered doses. No clinical or laboratory abnormalities were noted in the 10 patients studied.Acyclovir (ACV), 9-(2-hydroxyethoxymethyl)guanine, is a new antiviral agent that has been shown in vitro as well as in animal models to be effective against certain herpesvirus infections (2,4,5,9,11,13). The pharmacokinetics of ACV have been previously reported after 1-h infusions in man (3). This study examines single-dose pharmacokinetics and tolerance of ACV in humans after 1-and 6-h infusions at two dose levels.( to 5, 5 to 9, 9 to 13, 13 to 25, 25 to 48, and 48 to 72 h for the 1-h infusion; and 0 to 6, 6 to 10, 10 to 14, 14 to 24, 24 to 48, and 48 to 72 h for the 6-h infusion. We have found that freeze-thawing of samples over at least a 2-year period has no noticeable effect on radioimmunoassay-identifiable ACV (unpublished data).Toxicity surveillance. Patients were evaluated for renal, hepatic, and hematological function before dosing and at 3 days and 1, 2, and 3 weeks postinfusion. These studies included a complete and differential blood count, reticulocyte and platelet counts, analysis of serum for glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, creatinine, urea nitrogen, alkaline phosphatase, total bilirubin, uric acid, and glucose levels, and urinalyses. Patients were assessed for symptoms of drug toxicity daily for the initial 3 days postinfusion and then weekly for the next 3 weeks.Radioimmunoassay for ACV. Plasma and urine concentrations of ACV were determined by the radioimmunoassay procedure developed by Quinn et al.(12) and field tested and validated by Hintz et al. (6