(+)-Usnic acid is a secondary metabolite of lichens belonging to the Usnea genus. Usnea lichens and purified usnic acids have been used historically in traditional herbal medicine as bactericidal and antimicrobial agents. (+)-Usnic acid exhibits membrane proton uncoupling activity, which not only forms the mechanistic basis of its bactericidal action, but also has provided a rationale for its use as a fat-burning, weight-loss agent. Purified (+)-usnic acid has been marketed in the United States for this purpose either alone or in combination with other chemical agents. Use of some of these fat-burning products that contain (+)-usnic acid has resulted in serious liver damage. This study investigated the potential toxicity of (+)-usnic acid in male and female F344/N Nctr rats and B6C3F1/Nctr mice that were exposed via feed for 3 months. F344/N Nctr rats were administered 0, 30, 60, 120, 360, or 720 ppm in feed, while B6C3F1/Nctr mice were administered 0, 15, 30, 60, 180, or 360 ppm in feed. (Abstract Abridged).