We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation. Participants were 1,180 middle-aged and older adults from the Midlife in the United States (MIDUS) Biomarker Project (M age = 57.3 years, SD = 11.5; 56% female). A composite measure of inflammation was derived from 5 biomarkers: serum levels of C-reactive protein, interleukin-6, fibrinogen, E-selectin, and ICAM-1. Participants provided self-report data regarding ACEs, RLEs, current lifestyle indices (cigarette smoking, alcohol consumption, physical exercise, waist circumference), current depressive symptoms, and demographic/biomedical characteristics. We also used indices of hypothalamic-pituitary-adrenocortical outflow (12-hr urinary cortisol) and sympathetic nervous system output (12-hr urinary norepinephrine and epinephrine). Analyses indicated that ACEs and RLEs were independently associated with higher levels of inflammation, controlling for each other's effects. Their interaction was not significant. The results were consistent with the hypothesis that associations between ACEs and inflammation were mediated through higher urinary norepinephrine output, greater waist circumference, smoking, and lower levels of exercise, whereas higher waist circumference and more smoking partially mediated the association between RLEs and inflammation. In support of the stress accumulation model, ACEs and RLEs had unique and additive contributions to inflammation at midlife, with no evidence of synergistic effects. Results also suggested that norepinephrine output and lifestyle indices may help explain how prior stressors foster inflammation at midlife.