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Previous observations have suggested a role for nitric oxide in the activity of the globus pallidus, but this functional involvement has not yet been tested in vivo. The extracellular activity of single units of the globus pallidus was recorded, and neuronal nitric oxide synthase was inhibited by systemically administering 7-nitro-indazole to a group of anaesthetised rats. Forty-five per cent of cells responded with a decrease in the firing rate. In another group of rats, the microiontophoretic administration of 3-morpholino-sydnonimin-hydrocloride (a nitric oxide donor) induced an increase in neuronal firing rate (24/28 cells), whereas the administration of Nω-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) reduced the activity of pallidal neurones (8/11 cells). No electrophysiological differences between drug-sensitive and -insensitive neurones were evidenced. An excitatory role of nitric oxide in controlling the level of spontaneous activity of globus pallidus neurones is suggested, without any influence upon the discharge pattern.