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The spread of COVID-19 within any given country or community at the onset of the pandemic depended in part on the sheltering-in-place rate of its citizens. The pandemic led us to revisit one of psychology’s most fundamental and most basic questions in a high-stakes context: What determines human behavior? Adopting a Lewinian interactionist lens, we investigate the independent and joint effects of macro-level government policies and micro-level psychological factors—i.e., personality—on whether individuals sheltered-in-place. We analyzed data collected in late March and early April 2020 from 101,005 participants in 55 countries, a time period that coincided with the early and accelerating stage of the COVID-19 pandemic. This time period also contained substantial variation in the stringency of governmental policy towards sheltering-in-place, both between countries and within each country over time. Analyses revealed that personality and the stringency of governmental policies independently predicted sheltering-in-place rates. Policy stringency was positively related to sheltering-in-place. For the personality dimensions, openness, conscientiousness, agreeableness, and neuroticism all predicted higher rates of sheltering-in-place, whereas extraversion was negatively related to staying at home. In addition, two personality traits—openness to experience and neuroticism—interacted with governmental policy to predict whether individuals sheltered-in-place; openness and neuroticism each had weaker effects on sheltering-in-place as governmental policies became stricter. Theoretically, the findings demonstrate that individual differences predict behavior (i.e., sheltering-in-place) even when governments take strong action targeting that behavior. Practically, they suggest that even if governments lift their shelter-in-place restrictions, some individuals will shelter-in-place less than others.