Nicotine has previously been shown to affect both long-term potentiation (LTP) and long-term depression and to reverse age-related impairments of LTP in the hippocampus. Levels of proinflammatory cytokines are known to be elevated with age and to inhibit LTP. In the present study we have investigated the effects of three pro-inflammatory cytokines on nicotine-enhanced LTP in the rat hippocampus in vitro. In the presence of nicotine the inhibitory effect of interleukin-1 beta, interleukin-18 and tumour necrosis factor-alpha on LTP was eliminated. Furthermore, significant depotentiation of established LTP could not be obtained in slices treated with nicotine. These experiments demonstrate that nicotine can reverse the inhibitory effects of pro-inflammatory cytokines on LTP.