Chronic administration of cocaine (10 mg/kg, i.p., every 12 h for 10 consecutive days) produced a large decrease in tyrosine hydroxylase-staining axons and terminal boutons in the caudate nucleus in rats when examined 60 days after the final cocaine injection. This effect was quantitated using the Leitz data acquisition and display system (DADS) which revealed that there was a 63% decrease in tyrosine hydroxylase-positive processes in the caudate nucleus. In addition, this cocaine treatment regimen produced a large decrease in the number of tyrosine hydroxylase-positive staining neuronal perikarya in the pars compacta of the substantia nigra. Use of the Leitz-DADS system revealed that there was a 51% decrease in tyrosine hydroxylase-positive material in the substantia nigra. These data demonstrated that chronic administration of cocaine produced a long-term loss of tyrosine hydroxylase in both the cell bodies of the substantia nigra and the nerve terminals of the caudate nucleus. Further studies are required to determine whether the observed changes are due to degeneration of the neurons or some metabolic effect.