Agmatine (decarboxylated arginine) has been proposed as an endogenous ligand for non-adrenoceptor, imidazoline binding sites, but also binds to alpha 2-adrenoceptors. The interaction of agmatine with alpha 2-adrenoceptors was evaluated by studying the effect of agmatine on the firing rate of locus coeruleus (LC) neurones using extracellular recordings in anesthetized rats and rat brain slices. In vivo, local application of agmatine into the LC caused a slight and short-lasting increase in cell firing rate (P < 0.005). In vitro, agmatine failed to change the firing rate of LC neurones nor did it antagonize the inhibitory effect of noradrenaline on these cells. Since alpha 2-adrenoceptors are known to inhibit the firing of LC cells, we conclude that agmatine does not have agonist or antagonist properties at alpha 2-adrenoceptors of these neurones.