Abstract Adverse effects of excessive drinking are widespread in society. Understanding the factors that contribute to excessive alcohol consumption is crucial for improved prevention, education, and intervention. The goal of the Chicago Social Drinking Project (CSDP) is to evaluate the role of subjective and physiologic responses to alcohol in the escalation and maintenance of excessive drinking in adults. Our paradigm integrates human laboratory alcohol challenge with longitudinal assessment of drinking and related behaviors to discern whether alcohol responses predict future drinking problems and alcohol use disorder (AUD) symptoms. The CSDP has demonstrated that heightened sensitivity to alcohol stimulation and reward (liking, wanting) characterize young adult heavy drinkers (HD) versus light drinkers (LD) and these responses are primary predictors of future drinking progression and development of AUD over a decade later. This alcohol response phenotype is also evident in a newly-tested cohort of young adult AUD drinkers. Contrary to prevailing models of addiction propensity, our findings show a pervasive and sustained heightened sensitivity to alcohol stimulation and reward in excessive drinkers, and not low reward and negative reinforcement. In this award phase, we propose to further advance new discoveries and challenge existing paradigms by continuing to examine our high- retention cohorts in CSDP as well as enroll new cohorts. In Aim 1, we will extend a final follow-up wave in our existing HD and LD as well as extend follow-up in our ongoing young adult AUD cohort (N=398; >98% retention) to discern binge drinking severity, AUD symptoms, and drinking consequences during middle adulthood to evaluate the role of early-adult stimulating, rewarding, and sedating alcohol responses in predicting these behaviors. In Aims 2 and 3, we will enroll two new cohorts historically excluded from alcohol challenge research to provide potentially the most robust tests on the role of alcohol responses in excessive drinking. These include young adult HD with affective disorder (n=100) and older, chronic AUD drinkers (n=100; non-treatment-seeking), and their respective control groups (n=70 each), to determine if their alcohol response phenotype is characterized primarily by stimulation and reward sensitivity or by reward insensitivity and relief of negative affect or withdrawal states, as commonly theorized. These participants will undergo similar alcohol and placebo laboratory sessions and follow-up on drinking behaviors and AUD symptoms, as in established cohorts. As well-controlled research examining biphasic alcohol responses in clinically-relevant subgroups of comorbid and older AUD drinkers is lacking, determining their alcohol response phenotype offers a unique opportunity to test current theories of incentive-sensitization, reward sensitivity, and positive/negative reinforcement models of the development and maintenance of addictive behavior.