Background. Inflammatory proteins including interleukin-6 (IL-6) and C-reactive protein (CRP) have been associated with incident cognitive impairment, but little research has addressed their effects on the rate of cognitive change, and findings are mixed. The purpose of this study was to examine the relationship between serum levels of IL-6 and CRP and the rate of cognitive change across a range of cognitive domains in a sample of healthy older persons. Methods. Growth curve analysis was performed on data from the MacArthur Study of Successful Aging, a longitudinal cohort study of high-functioning older adults aged 70-79 years at baseline in 1988 and reinterviewed in 1991 and 1995 (N = 851). Individual growth curve parameters were derived from baseline and follow-up performance in abstraction, language, spatial ability, verbal recall, spatial recognition, and global cognitive function based on age, IL-6, CRP, and covariates. Results. Cross-sectionally, there is a generally linear negative relationship between inflammation and cognition, such that higher levels of inflammation are associated with lower levels of baseline cognitive function. After controlling for potential confounders, there was no effect of inflammation on baseline cognitive function or the rate of longitudinal cognitive change. However, persons in the top tertile on IL-6 were at an increased risk of incident declines on the Short Portable Mental Status Questionnaire (SPMSQ). Conclusions. Although high levels of inflammation are associated with incident cognitive impairment, these results do not generalize to the full range of cognitive changes, where the role of inflammation appears to be marginal.