Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (A) is involved in Alzheimers disease (AD), a neurodegenerative disorder leading to cognitive deficits. Nicotine, is also claimed to act as a cognitive enhancer. A is known to bind with high affinity to the 7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (i.c.v.) injection of the endogenous peptide A_1-40 on LTP in area CA1 of urethane-anaesthetised rats. We also examined the effect of A_12-28 (i.c.v.), which binds with high affinity to the 7-nAChR and the specific 7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that A_12-28 had no effect on LTP while MLA depressed significantly LTP suggesting that activation of the 7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with A_12-28 for binding to 7-nAChR it does not appear to modulate LTP. To determine if the depressive action of A_1-40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10nmol A_1-40 caused a significant depression of LTP while nicotine alone (3mg/kg) had no effect on LTP. Co-injection of nicotine with A_1-40 1 hour prior to LTP induction caused a further significant depression of LTP compared to A_1-40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by A_1-40. This then suggests that nicotine may exacerbate the depressive actions of A on synaptic plasticity in AD.