Initial pharmacokinetic and bioavailability data in man were obtained from a phase I, open-label, dose-escalating, multiple-dose study of intravenously and orally administered zidovudine. Dose-independent kinetics were observed over the dose-range 2.0 to 10 mg/kg (oral). Zidovudine is rapidly and extensively absorbed following oral administration. The mean half-life is approximately 1 h. The drug is capable of crossing the blood-brain barrier resulting in antiviral concentrations within the cerebrospinal fluid. The major route of elimination is by hepatic glucuronidation followed by rapid excretion of the metabolite in the urine. Consequently, factors affecting liver or kidney function may alter the pharmacokinetic profile. Although no systematic studies of potential drug interactions have been reported, data are accumulating on the concomitant use of zidovudine with other medications.