OBJECTIVE To determine the association among aging, inflammation, and cytokine production by peripheral blood mononuclear cells. METHODS We examined production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-1 receptor antagonist (IL-1Ra), and IL-6 in 711 elderly participants in the Framingham Heart Study (mean age, 79 y) and 21 young healthy volunteers (mean age, 39 y). The elderly subjects were categorized by serum C-reactive protein (CRP) concentration, a marker of systemic inflammation. RESULTS Production of IL-6 (p < .00001) and IL-1Ra (p < .00001) was higher in the elderly subjects than in the control group. IL-6 production increased with increasing CRP, whereas IL-1RA was uniformly elevated in elderly subjects regardless of CRP. However, we found no difference in the production of IL-1 beta or TNF-alpha between the young and elderly groups, regardless of CRP status. IL-6 population correlated with IL-1 beta (r = .36, p < .0001) and TNF-alpha production (r = .25, p < .0001), but IL-1Ra production did not. CONCLUSIONS Production of IL-6 and IL-1Ra--but not IL-1 beta or TNF-alpha--was increased in the elderly compared to healthy, young subjects. The increase in IL-6 also correlated with increased production of CRP, a marker of inflammation. However, IL-1Ra was increased in the elderly independently of CRP production. Although limited by the small control group, these data suggest that dysregulation of some inflammatory cytokines occurs with age, but the role of inflammation in aging remains unclear.