We compared the effect of mecamylamine and fluoxetine on the hippocampal noradrenaline (NA) release evoked by nicotine in vitro. Nicotine (100 microM) increased the basal release of [3H]NA from rat hippocampal slices. This effect was blocked by the potent nicotinic antagonist mecamylamine in a dose-dependent manner (IC50 = 0.19 microM). The selective serotonin reuptake inhibitor (SSRI) fluoxetine also antagonised the response to nicotine in a dose-dependent manner with a similar strength (IC50 = 0.57 microM). Our data indicate that fluoxetine has nicotinic acetylcholine receptor antagonist effect in the central nervous system. The possible clinical significance of this finding is discussed.