Background: Physical activity and fitness in adolescence may improve cognition in adulthood by increasing insulin-like growth factor I (IGF-I). Methods: As part of the Amsterdam Growth and Health Longitudinal Study, following subjects from age 13 to 42 years, physical activity and fitness of 303 subjects were assessed annually between the ages 13 to 16. At mean age 36, physical activity, fitness and IGF-I were measured. At mean age 42, IGF-I and cognitive factors (ie, executive functioning and visual-spatial memory) were measured. The linear regression of physical activity and fitness in adolescence and IGF-I in adulthood on cognitive scores in adulthood was investigated. Results: A significant association was found in males between physical activity in adolescence and executive function in adulthood (Spatial Working Memory Between Errors: β = -.18, B = -.13, 95% CI = -.259 to -.010; Spatial Working Memory Strategy: β = -.20, B = -.08, 95% CI = -.147 to -.014). No association between physical activity or fitness in adolescence and cognitive function in adulthood was found in females, nor any intermediate role for IGF-I in either sex. Conclusions: The results suggest a stimulating effect of adolescent physical activity in males on executive functions in adulthood, emphasizing the importance of an active lifestyle among adolescent males.