The effect of exogenous GM1 ganglioside on selectively noradrenaline-denervated rat cerebral cortex was investigated by measuring the spatial distribution of endogenous noradrenaline levels and by fluorescence histochemical analysis. A local noradrenaline denervation was produced by intracortical infusion of the selective catecholamine neurotoxin 6-hydroxydopamine for 3 or 7 days. The neurotoxin infusion caused an almost complete noradrenaline denervation in a restricted area around the infusion point as reflected by an almost complete long-term disappearance of noradrenaline nerve terminals and reduction of noradrenaline levels. There was with time a slow recovery of the levels, most likely related to a spontaneous noradrenaline nerve terminal regeneration. Post-treatment for 1 week with GM1 had very small effects on the 6-hydroxydopamine-induced reduction of the noradrenaline levels, while pretreatment with GM1 for 3 days before the neurotoxin infusion and continuing the GM1 administration for another 7-14 days significantly enhanced noradrenaline recovery, as observed both bio- and histochemically. GM1 had no effect on the 6-hydroxydopamine-induced noradrenaline depletion acutely, indicating that GM1 does not interfere with the direct neurotoxic actions of 6-hydroxydopamine. The present results thus indicate that exogenous GM1 enhances regrowth of noradrenaline nerve terminals which may be due to a regrowth stimulatory effect (regeneration/collateral sprouting) and/or related to protective actions of GM1 against retrograde degeneration of noradrenaline axons following the neurotoxin-induced lesion.