Recent evidence indicates that the pro-inflammatory cytokines (PICs) can affect learning and memory processes. To examine the effect of the PICs on leverpress escape/avoidance conditioning, we injected male Sprague-Dawley rats with IL-1beta, IL-6 (both 3.0 microg/kg, i.p.), TNFalpha (6.0 microg/kg, i.p.) or vehicle, 24h before a single 4-h session of leverpress escape/avoidance conditioning. The TNFalpha-treated animals made more avoidance responses and fewer escape responses than controls during the last hour of the session. Further, both TNFalpha- and IL-1beta-treated animals had a higher percent avoidance than controls during the 4th hour of the session. None of the cytokines had an effect on the number of leverpresses during safety, a putative measure of anxiety. Results are discussed in terms of the differential central effects of the pro-inflammatory cytokines and the possible relationship to avoidance conditioning.