This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations that highlighted recent studies conducted using the clamp including: (1) determination of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination of family history of alcoholism, recent drinking history, and levels and rates of administration as determinants of the response to alcohol and risk for alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4) a study of the effects of steady-state blood alcohol levels on auditory event-related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future directions for research using the alcohol clamp.