The pleiotropic cytokine, interleukin-6 (IL-6), has emerged as a key factor in the biology of aging and the physiology of inflammation. Yet much of what we know about the normal functioning of IL-6 has been generated primarily from research on European populations and Americans of European descent. Our analyses compared IL-6 levels in 382 middle-aged and older Japanese to the values found in 1209 Caucasian- and African-Americans from the Midlife in the United States survey (MIDUS). Across the life span from 30 to 80. years of age, mean IL-6 levels were strikingly lower in Japanese individuals. Significantly lower levels of C-reactive protein (CRP) and fibrinogen (FBG) provided confirmatory evidence for a population difference in proinflammatory activity. Because IL-6 release has been associated with obesity, differences in body mass index (BMI) were taken into consideration. Japanese had the lowest, and African-Americans had the highest overall BMIs, but significant group differences in IL-6 persisted even after BMI was included as a covariate in the analyses. Additional support for distinct variation in IL-6 biology was generated when systemic levels of the soluble receptor for IL-6 (sIL-6r) were evaluated. Serum sIL-6r was higher in Japanese than Americans, but was most notably low in African-Americans. Our cytokine data concur with national differences in the prevalence of age-related illnesses linked to inflammatory physiology, including cardiovascular disease. The findings also highlight the importance of broadening the diversity of people included in population studies of health and aging, especially given the relative paucity of information for some Asian countries and on individuals of Asian heritage living in the US. © 2010 Elsevier Inc.