Study Objective: To examine the pharmacokinetics of zidovudine during the menstrual cycle in human immunodeficiency virus- (HIV-) positive women., Design: Open, unblinded study., Setting: A women's clinic for acquired immunodeficiency syndrome (AIDS) at a large medical center., Patients: HIV-positive women with a CD4+ cell count above 200/mm3, receiving long-term zidovudine therapy, with a history of regular menstrual cycles., Interventions: All patients received a 100-mg dose of zidovudine in the fasted state on three occasions., Measurements and Main Results: Zidovudine and zidovudine-glucuronide plasma concentrations were measured with radioimmunoassay to determine the pharmacokinetic characteristics during each menstrual phase. The drug's mean peak plasma concentrations (range 233-808 ng/ml) were 556 +/- 145, 385 +/- 132, and 495 +/- 143 ng/ml during the menstrual, late follicular-ovulatory, and luteal phases, respectively. Initially, plasma concentrations declined in a linear fashion from 0 to 4 hours, with a prolonged elimination phase in many patients after 4 hours. The mean zidovudine area under the curve was 886 +/- 156, 845 +/- 268, and 775 +/- 167 ng.hour/ml. The mean percentage of dose recovered was 44.2 +/- 26.0, 56.9 +/- 19.1, and 42.2 +/- 16.6, respectively., Conclusions: The pharmacokinetics of zidovudine were not different during the three phases of the menstrual cycle; however, considerable intrapatient and interpatient variability was noted for many of the values.