Despite a well-documented gender pattern in adolescent mental health, research investigating possible explanatory factors from a gender-theoretical approach is scarce. This paper reports a grounded theory study based on 29 focus groups. The aim was to explore 16- to 19-year-old students' perceptions of what is significant for mental health, and to apply a gender analysis to the findings in order to advance understanding of the gender pattern in adolescent mental health. Significant factors were identified in three social processes categories, including both positive and negative aspects: (1) social interactions, (2) performance and (3) responsibility. Girls more often experienced negative aspects of these processes, placing them at greater risk for mental health problems. Boys' more positive mental health appeared to be associated with their low degree of responsibility-taking and beneficial positions relative to girls. Negotiating cultural norms of femininity and masculinity seemed to be more strenuous for girls, which could place them at a disadvantage with regard to mental health. Social factors and processes (particularly responsibility), gendered power relations and constructions of masculinities and femininities should be acknowledged as important for adolescent mental health.