Academic self-concept is one's perception of his or her ability in an academic domain and is formed by comparing oneself to other students. As college biology classrooms transition from lecturing to active learning, students interact more with each other and are likely comparing themselves more to other students in the class. Student characteristics can impact students' academic self-concept; however, this has been unexplored in the context of undergraduate biology. In this study, we explored whether student characteristics can affect academic self-concept in the context of an active learning college physiology course. Using a survey, students self-reported how smart they perceived themselves to be in the context of physiology relative to the whole class and relative to their groupmate, the student with whom they worked most closely in class. Using linear regression, we found that men and native English speakers had significantly higher academic self-concept relative to the whole class compared with women and nonnative English speakers. Using logistic regression, we found that men had significantly higher academic self-concept relative to their groupmate compared with women. Using constant comparison methods, we identified nine factors that students reported influenced how they determined whether they were more or less smart than their groupmate. Finally, we found that students were more likely to report participating more than their groupmate if they had a higher academic self-concept. These findings suggest that student characteristics can influence students' academic self-concept, which in turn may influence their participation in small-group discussion and their academic achievement in active learning classes.