This study examined the effects of kainic, ibotenic, and quisqualic acid-induced lesions of the rat striatum on biochemical markers of the glutamatergic corticostriatal and dopaminergic nigrostriatal afferent transmissions. Fifteen to 21 days after striatal injections of these various compounds, significant reductions in the high-affinity glutamate uptake rate, due to decreases in the Vmax of the transport process, were measured. Interestingly, the relationship between these decreases in the Vmax and the decreases in the levels of biochemical markers for the intrinsic striatal cholinergic and GABAergic neurons differed depending on the excitotoxin used. These findings suggest that excitatory amino acid agonists-induced alterations of the glutamatergic terminal activity may not depend only on the loss of cholinergic and GABAergic striatal neurons. In contrast, the observed changes in the dopamine and metabolite contents seemed to be related to the extent of the striatal neuronal degeneration induced by each excitotoxin. All in all, these results indicate that excitatory amino acid agonists can impair the activity and/or the integrity of the two main striatal afferent pathways, through presumably different mechanisms.