BACKGROUND: Systemic chronic inflammation has been found to be related to all-cause mortality risk in older persons. We investigated whether specific chronic conditions, particularly cardiovascular disease (CVD), affect the association between high interleukin (IL)-6 level and mortality in a sample of disabled older women. METHODS AND RESULTS: IL-6 serum level was measured at baseline in 620 women >/=65 years old. The presence and severity of medical conditions was ascertained by standard criteria that used multiple sources of information. The sample was surveyed over the 3-year follow-up. After adjustment for potential confounders, compared with those in the lowest tertile, women in the highest IL-6 tertile were at higher risk of all-cause mortality. The presence of CVD, however, strongly affected the risk of mortality associated with high IL-6. Among women with prevalent CVD, those with high IL-6 levels had >4-fold risk of death (RR 4.6; 95% CI 2.0 to 10.5) compared with women in the lowest tertile, whereas the relative risk associated with high IL-6 among those without CVD was much lower and not significant (RR 1.8; 95% CI 0.7 to 4.2). Adjustment for all chronic diseases and disease severity measures, including ankle-brachial index, forced expiratory volume, and exercise tolerance, did not change the results. CONCLUSIONS: IL-6 level is helpful in identifying a subgroup of older CVD patients with high risk of death over a period of 3 years. Systemic inflammation, as measured by IL-6, may be related to the clinical evolution of older patients with CVD.