PROJECT SUMMARY/ABSTRACT Alcohol use poses significant health problems particularly when characterized by bouts of heavy consumption (i.e., binges). It is now recognized that women demonstrate greater vulnerability to the adverse effects of alcohol, including greater physiological risk of organ damage (e.g., liver cirrhosis), than do men with comparable histories of alcohol use. Research suggests that ovarian hormones play a role in substance abuse. With regard to alcohol use, there is evidence to suggest that women may exhibit distinct patterns of heavy drinking across the menstrual cycle. Indeed, our preliminary research shows that surges in follicular estradiol [E2] at ovulation predict increased alcohol use in young women. Yet, to date no research has aimed to determine the specific behavioral mechanisms by which rapid surges in E2 confer increased abuse potential of alcohol. The proposed study directly examines ovarian hormone flux and acute sensitivity to alcohol to provide the first rigorous and integrative test of the hypothesis that rapid rises in estradiol increase the acute rewarding and disinhibiting effects of alcohol and that this heightened sensitivity increases alcohol use outside the laboratory. A sample of 100 naturally-cycling women will be examined daily over their menstrual cycle using an integrative combination of daily ecological assessments of hormone fluctuations and alcohol use along with strategically-timed laboratory tests of their acute sensitivity to the rewarding and disinhibiting effects of a controlled dose of alcohol. The findings will advance understanding of the neurobehavioral mechanisms linking E2 to alcohol abuse and inform clinical assessment practice by highlighting the importance of menstrual cycle phase and hormonal profiles when assessing alcohol abuse risk in young women.