Unilateral lesioning of the rat locus coeruleus by an electric current (0.3 mA/10 s) reduces the ipsilateral hippocampal tissue content of dopamine (DA) and noradrenaline (NA) by 80% and 60% respectively, and protects against the excitotoxic action of bilateral kainate injections (1.1 nmol/mu-l) in the hippocampus. On the ipsilateral side hippocampal CA1, CA2 and DG cells were protected; lesser protection of CA1 cells was seen on the contralateral side. The unilateral injection of 6-hydroxydopamine (8.8-mu-g/2-mu-1/5 min) into the medial forebrain bundle abolishes the increase in extracellular NA concentration induced by kainate in the ipsilateral hippocampus without altering the low extracellular DA levels. This medial forebrain bundle lesion protects (on the ipsilateral side) against kainate toxicity (500-mu-M through the probe for 20 min) in the hippocampus (CA1, CA2 and DG cells). The noradrenergic innervation of the hippocampus apparently potentiates the excitotoxic effect of focal injection of kainate.