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Background U.S. border populations have been found to be at high risk for alcohol problems. However, results from the U.S.-Mexico Study on Alcohol and Related Conditions ( UMSARC) revealed surprisingly large variation in alcohol outcomes even among Texas border sites, with alcohol use disorder ( AUD) prevalence ~1.5 to 1.6 times greater in the border city of Laredo compared to both San Antonio and the border site of McAllen/Brownsville. Because a better understanding of this variation is important to identifying environmental influences on AUD, we developed and tested a conceptual model addressing variation in AUD prevalence across Texas UMSARC sites. Methods Surveys involved in-person, household interviews with Mexican-origin residents of the Texas border cities Laredo ( n = 751) and McAllen/Brownsville ( n = 814), with San Antonio as an off-border comparison ( n = 771). Interviews assessed past-year DSM-5 AUD; past-year heavy drinking; coping and enhancement motives; and 7 indicators of substance use climate and stress exposure hypothesized to mediate site effects. Analyses, conducted separately by gender, included regressions and structural equation modeling with Mplus. Results Preliminary analyses revealed that site effects on AUD prevalence were, unexpectedly, exclusive to men, and that Laredan men were similar to McAllen/Brownsville men on demographics, acculturation, and cross-border mobility. However, sites differed dramatically on most of the hypothesized risk factors. Structural equation models confirmed that site effects on AUD were partially mediated via effects of site on indicators of a permissive climate (i.e., permissive drinking norms, high drug availability) and stress exposures (i.e., high exposure to violence/crime, low family support), and via downstream effects on drinking motives and heavy drinking. Conclusions Findings of very high rates of past-12-month AUD among Laredan men (35%) suggest the possibility of significant heterogeneity even within demographically similar border areas and underline the need for additional study of the border region. Findings regarding our conceptual model suggest that this model may constitute a useful initial framework for future research on alcohol problems at the border. However, additional research using representative samples is needed to confirm and expand this model to comprehensively address relevant individual and community factors. [ABSTRACT FROM AUTHOR]