The pharmacokinetics of D(+)-usnic acid--a lichen antitubercular, antitumor, and enzyme-inhibiting agent--was studied in rabbits following intravenous or oral administration of 5 and 20 mg/kg body weight doses, respectively. Plasma samples were collected at different time intervals, and usnic acid was determined by HPLC. Plasma usnic acid levels following intravenous administration showed a triexponential elimination with a mean +/- SD terminal half-life of 10.7 +/- 4.6 hr. The volume of distribution of the central compartment and systemic clearance were 43.9 +/- 21.3 ml/kg and 12.2 +/- 3.0 ml/hr/kg, respectively. Pharmacokinetic parameters obtained, based on compartmental and noncompartmental approaches, were comparable. Plasma concentration data obtained after oral administration were analyzed using a noncompartmental method. Peak plasma level (Cmax) of 32.5 +/- 6.8 micrograms/ml was achieved in 12.2 +/- 3.8 hr (tmax). Mean absolute bioavailability of usnic acid following oral administration was 77.8%.