Excitotoxicities of glutamate and NMDA were studied on primary cultures of rat embryonic substantia nigra. The toxicity of the general neuronal population (identified with neuron specific enolase-NSE) was compared with that of dopaminergic neurons (identified with TH antibodies). We have shown that there exists a time-dependent toxicity to glutamate in 9 d old cultures in vitro and exposures as short as 5 min are significantly toxic. By comparing the effects of long time exposures (24 h) to NMDA and glutamate, we can show dose-dependent toxicity; however NMDA shows a less marked effect, especially at high doses (> 500-1000 microM) as opposed to less potent lower doses (< 500 microM). In comparison to the general population of NSE-positive mesencephalic neurons, TH-positive neurons seem to exhibit a similar vulnerability to EAA. The fact that TH-positive neurons are only partially protected against glutamate toxicity by the non-competitive NMDA antagonist TCP indicates that they are more susceptible to non-NMDA mediated neurotoxicity than the general neuronal population.