1This study attempted to determine whether the activation of the tryptophan carrier in rat forebrain synaptosomes caused by depolarization or by extracellular sodium depletion occurred exclusively in 5-hydroxytryptaminergic nerve endings. 2 Ascending 5-hydroxytryptaminergic neurones were lesioned either electrolytically or by intraventricular administration of 5,7-dihydroxytryptamine. The extent of the lesion was assessed by comparing the uptake of [3H]-5-hydroxytryptamine (5-HT) in lesioned animals and in sham-operated controls.[3H]-5-HT uptake was reduced by 85.9 + 1.63% (mean + s.e.mean) in animals receiving electrolytic lesions, and by 87.4 + 4.51% in those receiving 5,7-dihydroxytryptamine. 3 The uptake of [3H]-tryptophan by synaptosomes from lesioned animals incubated in standard Na+-rich media was slightly lower (278.8 + 27.3 pmol mg-1 protein min-') than that observed in shamoperated controls (360.6 + 30.3 pmol mg'-protein min-). However, uptake in the absence of extracellular Na+ was increased to a similar extent in both the sham-operated (539 + 54.5pmolmg-protein min -1) and lesioned animals (507.2 + 42.4 pmol mg-1 protein min -1).