Although estrogen replacement therapy (ERT) has proven highly effective in preventing both the short- and long-term adverse clinical outcomes associated with menopause, it is important to recognize that the pharmacokinetic and metabolic effects of ERT vary with dosage and route of delivery. One of the most promising methods of administering ERT is the transdermal therapeutic system (TTS), or "patch," the efficacy of which is comparable to that of other forms of ERT, but whose unique pharmacokinetic profile may confer several distinct clinical advantages over the oral route. The present article addresses some of the key pharmacokinetic and metabolic differences between these two dosing forms, with particular emphasis on their respective effects on gonadotropins, hemostasis and coagulation, lipid metabolism, hepatobiliary function, and bone. An extensive review of clinical experience accrued over the past decade suggests that transdermal ERT is a viable alternative to oral ERT.