Goldenseal root was identified as the most potent inhibitor of CYP3A4 in a study that tested 21 popular herbal products for in vitro inhibitory activity. The purpose of this investigation was to examine the influence of goldenseal root on the disposition of the CYP3A4 substrate indinavir in humans. Using a crossover study design, the pharmacokinetics of indinavir were characterized in 10 healthy volunteers before and after 14 days of treatment with goldenseal root (1140 mg twice daily). Indinavir was given as a single 800-mg oral dose, and blood samples were collected for 8 hours following the dose. No statistically significant differences in peak concentration (11.6 vs. 11.9 mg/L) or oral clearance (26.8 vs. 23.9 mg*h/L) were observed following treatment with goldenseal root. Half-life and time to reach peak concentration were also unchanged by goldenseal. These results suggest that patients being treated with indinavir can safely take goldenseal root and that interactions with other drugs metabolized by CYP3A4 in the liver are unlikely.