The generation of the novel messenger molecule nitric oxide (NO) has been demonstrated in many tissues across phyla including nervous systems. It is produced on demand by the enzyme nitric oxide synthase often stimulated by intracellular calcium and typically affecting guanylate cyclase thought to be its principal target in an auto and/or paracrine fashion. This results in the generation of the secondary messenger cyclic guanosine monophosphate (cGMP). Nitric oxide synthase has been demonstrated in various mollusk brains and manipulation of NO levels has been shown to affect behavior in mollusks. Apart from modulation of the effect of the peptide GSPYFVamide, there appears little published on direct or modulatory effects of NO on Helix aspersa central neurons. We present here initial results to show that NO can be generated in the region around F1 in the right parietal ganglion and that NO and cGMP directly hyperpolarize this neuron. For example, application of the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP; 200 µM) can cause a mean hyperpolarization of 41.7 mV, while 2 mM 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) produced a mean hyperpolarization of 33.4 mV. Additionally, pre-exposure to NO-donors or cGMP appears to significantly reduce or even eliminates the normal hyperpolarizing K(+)-mediated response to dopamine (DA) by this neuron; 200 µM SNAP abolishes a standard response to 0.5 µM DA while 1 mM 8-bromo-cGMP reduces it 62%.