The psychostimulants cocaine and methamphetamine produce their euphoric effects through an interaction with the mesolimbic dopamine system. Methamphetamine, unlike cocaine, has been shown to be neurotoxic to both dopaminergic and serotonergic systems. We have previously determined that a 6 day exposure to methamphetamine causes neuronal damage to tyrosine hydroxylase-immunopositive cells in our tissue culture model of the mesencephalon. Over the same exposure period, cocaine neither impaired neuronal function nor altered dopamine cell survival. To test whether a longer exposure period to cocaine would alter dopamine function, we added cocaine (100 microM) to the cultures once daily for either 8 or 11 days and examined changes in dopamine uptake, cell survival and morphology 24 h after the last administration. Cocaine did not produce any signs of neurotoxicity in the mesencephalic cultures.