To facilitate studies of the pharmacokinetic properties of zidovudine, the relationship between plasma and salivary concentrations of the drug was studied, after oral dosage, in 10 HIV-infected patients. Zidovudine concentrations were determined in plasma, unstimulated mixed saliva and citric-acid-stimulated mixed saliva over a period of 3± hours by high-performance liquid chromatography. Correlation coefficients were r = 0.97 (P < 0.0001) for stimulated saliva compared with plasma and r = 0.89 (P < 0.0001) for unstimulated saliva, with average values in unstimulated saliva being 113.8 ± 44.6% in plasma and 67.8 ± 25.4% in stimulated saliva. Stimulated saliva values found to be 70% of the total reflected the concentration of the unbound drug in plasma. Except for a shorter half-life time (t) in saliva, pharmacokinetic parameters showed a good correlation in the three types of specimen. These findings and the convenience of sample collection suggest that citric-acid-stimulated saliva might be an appropriate specimen for monitoring zidovudine therapy.