Exercise has acute, positive effects on mood and can lead to antidepressant effects over time when repeated regularly. The mechanisms underlying the antidepressant effects of exercise training are not well known, limiting the prescription of exercise training for depression. Serum Insulin-Like Growth Factor-1 (IGF-1) appears dysregulated in those with Major Depressive Disorder (MDD), suggesting MDD could inhibit or alter the IGF-1 response to exercise. In healthy individuals, exercise has been shown to acutely increase serum IGF-1, which may act positively on the dysregulated IGF-1 system in MDD. Therefore, the purpose of this study was to examine the sensitivity of serum IGF-1 levels to an acute maximal exercise bout in adults with MDD and healthy controls. Additionally, clinical and behavioral factors of MDD are likely to affect this system, such as depression severity, antidepressant usage and physical activity habits. Baseline data were used from a larger trial in Germany (SPeED Study) collected from individuals with mild to moderate MDD (n=113) and healthy controls (n=34) that were matched for age, sex, and education. Demographics, depression severity (Hamilton Depression Rating Scale-17), self-reported antidepressant usage, MVPA (International Physical Activity Questionnaire-Short Form), and blood draws before and after a maximal exercise test were collected. Multiple linear regressions were conducted to determine relationships between depression severity, antidepressant usage, and physical activity with peripheral IGF-1 levels following acute exercise. Covariates included demographic factors and IGF-1 pre-exercise (baseline levels). Acute IGF-1 changes occurred similarly in depression (mean ± SD; 11.3 ± 12.9) as well as healthy adults (11.3 ± 20.4: p>0.05). Neither depression severity, antidepressant use, nor regular physical activity were significant predictors of peripheral IGF-1 levels at baseline or following exercise. Individuals with MDD are likely to have favorable exercise-induced IGF-1 changes regardless of clinical and behavioral differences. Acute exercise increases peripheral IGF-1 briefly, and in response to repeated exercise bouts, the IGF-1 system could normalize over time. The normalization of the IGF-1 system might be a possible mechanism underlying mood increases that occur during exercise with exercise training research warranted.