This thesis is part of the School in Motion study. School in Motion was initiated by the Norwegian government because of the political demand for more knowledge regarding possible approaches to increase adolescent physical activity. The reason for the demand was a report depicting 15-year-olds as among the most sedentary populations in Norway. This is concerning because physical activity can have a preventive function against non-communicable diseases, psychological difficulties and mental disorders. Norwegian schools are given extended responsibilities for their students’ physical and mental health. Physical activity can contribute in this purpose, therefore, finding feasible approaches to increase physical activity in school is an important research topic. The School in Motion study was a cluster randomized controlled trial involving 29 lower secondary schools in Norway. The participants were 2084 9th graders (14-15 years old) from schools located in western, south western, southern, and eastern parts of the country. The study aimed to implement two separate intervention models for increased physical activity and physical education in school, in order to evaluate their effects on physical activity, physical health, mental health, learning and learning environment. Intervention model 1 included weekly, 30 minutes of physical activity, 30 minutes of physically active academic lessons, and one additional physical education lesson. Intervention model 2 included two weekly physical activity lessons in which students were encouraged to pursue their own activity interests, in groups they formed themselves. The aims of this thesis were to elucidate different aspects of the relationship between school-based physical activity interventions, physical fitness and mental health among adolescents, and the feasibility of school-based PA interventions in lower secondary school. The data that are presented in this thesis are the basis of four separate papers. The first paper analyzed baseline data to examine the cross-sectional association between physical fitness and mental health. The results showed a small, inverse association between cardiorespiratory fitness and mental health, while no association was found between mental health and body composition or muscular strength. The second paper presents data from a qualitative study that aimed to elucidate how intervention model 2 was implemented, and what influenced the implementation. The results showed large differences in how the intervention was implemented. Specifically, two out of four investigated schools implemented the intervention adequately, one school implemented the intervention partially adequate and the last school failed at several implementation aspects. Four main factors were responsible for influencing implementation: frame factors, intervention-, participant-, and provider characteristics. The results elucidate the challenge of implementing a complex physical activity intervention in schools, i. e., complex contexts, and expecting the implementation process to be similar for the schools. The third paper examined the effect the interventions had on mental health, by using a cluster randomized controlled trial design. The results showed no intervention effects on the overall population. However, subgroup analyses indicated that intervention model 1 was beneficial for those with high levels of psychological difficulties at baseline, and both intervention models were beneficial for the immigrant subgroup. The results also indicated that intervention model 2 had a negative effect on a subscale of psychological difficulties, peer relationships, within the subgroups non-immigrant girls, and those with “borderline” psychological difficulties at baseline. The fourth paper presents associations between the one-year change in physical fitness components and mental health status. Subgroup analyses showed an inverse association between change in cardiorespiratory fitness and mental health status among boys; an inverse association between change in muscular strength and mental health status among immigrants; and an association between change in cardiorespiratory fitness and mental health among girls with high socioeconomic status. The results indicate that the associations between physical activity, physical fitness and mental health among adolescents depend on different mechanisms that are specific to certain subgroups. The findings of this thesis add nuance to a research field characterized by relatively few studies, small sample sizes, cross-sectional designs and little qualitative knowledge. In summary, this thesis suggests that improving cardiorespiratory fitness can be beneficial for mental health promotion among adolescent boys; and that improving muscular strength can be beneficial for mental health promotion among adolescent immigrants. Moreover, school-based PA programs can be useful for mental health promotion among adolescents with high levels of psychological difficulties and among adolescent immigrants. Regarding the implementation of physical activity programs in schools, this is feasible. However, a successful implementation depends to a large degree on schools’ facilities and frame factors, thus, the physical activity programs should have flexible designs to secure an optimal fit in each individual school. The new Core curriculum in Norway for primary and secondary education specifies that physical and mental health is to be an important interdisciplinary topic in school. The knowledge generated through this thesis can contribute to the development of this interdisciplinary topic, and to the ongoing discussion about the role of physical activity and mental health in school.