Levels of circulating cytokines were measured in 22 hospitalized patients with pneumococcal infections during the first week after admission, to test for age-associated differences. Twenty-two healthy age- and sex-matched subjects were included as controls. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-1 receptor antagonist, soluble TNF receptor I (sTNFR-I), and IL-10 were increased on admission (P<.05), but macrophage inflammatory protein (MIP)-1beta was not. Whereas levels of cytokines were similar on admission, levels of TNF-alpha and sTNFR-I after 1 week were higher (P<.05) in elderly (68-91 years) than in young (37-55 years) patients. Furthermore, plasma levels of IL-10 and sTNFR-I after 1 week were positively correlated with age, and the declines in sTNFR-I and in the TNFalpha/IL-10 ratio from day 0 to day 7 were correlated with age. Thus, aging was associated with prolonged inflammatory activity. This may reflect decreased ability to control the infection or a dysregulated cytokine response.