The use of herbal medicine has become increasingly popular in the United States. Hypericum perforatum (St. John's wort) is an herbal extract that is used widely as a folk remedy for depression. In this case report, we describe a kidney transplant recipient who developed marked reduction of cyclosporine therapeutic activity after the self-initiation of St. John's wort. Postulated mechanisms for the ability of this herbal extract to interact with pharmaceutical medications are presented, and the existing literature is reviewed.