Growing evidence suggests that 'pro-inflammatory' cytokines such as TNF play a role in cognitive processes and in aging. To test the effects of TNF on cognitive function throughout aging, we used transgenic mice which were TNF deficient. We then tested these mice along with wild-type mice, at 3, 6 and 12 months of age, using the Barnes maze. Wild-type controls showed better memory than TNF knock-out mice at 3 months of age, but not at 6 and 12 months of age. Results of our experiment show that endogenous TNF plays an important role in cognitive processes throughout aging processes. The implications of these findings are far-reaching and include a possible role for cytokines in the molecular and cellular mechanisms subserving age-related changes in learning, memory and cognition.