Herbal therapies are widely used, but there are few data on their interactions with conventional medications. This study evaluated the effect of garlic supplements on the pharmacokinetics of saquinavir. Ten healthy volunteers received 10 doses of saquinavir (Fortovase) at a dosage of 1200 mg 3 times daily with meals for 4 days on study days 1-4, 22-25, and 36-39, and they received a total of 41 doses of garlic caplets taken 2 times daily on study days 5-25. Blood samples were obtained on study days 4, 25, and 39 for determination of saquinavir plasma pharmacokinetic parameters. In the presence of garlic, the mean saquinavir area under the curve (AUC) during the 8-h dosing interval decreased by 51%, trough levels at 8 h after dosing decreased by 49%, and the mean maximum concentrations (Cmax) decreased by 54%. After the 10-day washout period, the AUC, trough, and Cmax values returned to 60%-70% of their values at baseline. Patients should use caution when combining garlic supplements with saquinavir when it is used as a sole protease inhibitor.