The mechanism of striatal damage induced by 3-nitropropionic acid (3-NPA) was studied in rats by neuropathological and neurochemical methods. Neuronal shrinkage with astrogliosis was observed in striatum after local injection of 0.5-5 mumol 3-NPA. Decortications involving dorsal and lateral aspects of frontal cortex or both frontal and parietal cortices significantly decreased the severity of striatal injuries induced by 3-NPA. This result suggests that corticostriatal projections play an important role in the development of striatal damage. No significant increase of glutamate and aspartate in striatal dialysates was observed, which indicated that 3-NPA may affect the postsynaptical sites and make the striatal neurons more vulnerable to endogenous levels of glutamate. Both of these findings suggested that 3-NPA produces indirect excitotoxic lesion to striatum. An increase of dopamine found in striatal dialysates may also be related to the occurrence of striatal damage.