The present study investigated the role of nicotinic receptors in the lateral septum in the modulation of anxiety. The effects of direct injections of nicotine into the lateral septum were first investigated in two tests of anxiety, social interaction and elevated plus-maze tests. Intra-septal injection of nicotine (1 and 4 microgram) induced consistent anxiogenic effects in both tests. The reversal of nicotinic effects with mecamylamine was then studied in the social interaction test. Intra-septal injection of mecamylamine at a low dose (15 ng) induced an anxiolytic effect, suggesting the presence of intrinsic cholinergic tone increasing anxiety. At higher doses (30-50 ng), mecamylamine was without effect in the social interaction test, but blocked the anxiogenic effects of nicotine (4 microgram). These findings provide further evidence for the role of the lateral septum in the modulation of anxiety and suggest that cholinergic projections to this brain area facilitate anxiety through nicotinic receptors.