Agricultural exposure to the organomanganese fungicide MANEB (manganese-ethylene-bis-dithiocarbamate) may induce an extrapyramidal syndrome resembling parkinsonism. To evaluate the relative role of manganese (Mn) and ethylene-bis-dithiocarbamate (EBDTC) in the hazard of organomanganese fungicides, we studied the effects of MANCOZEB (Mn-Zinc-EBDTC) and ZINEB (Zinc-EBDTC) on serumless dissociated mesencephalic-striatal primary coculture. High affinity 3H-dopamine (DA) and 14C GABA uptakes as well as immunocytochemical staining of tyrosine hydroxylase (TH)-containing cells were used as specific functional markers of DA and GABA neuron viability. Both MANCOZEB and ZINEB, at 10 and 50 microM concentrations, dose dependently reduced DA and GABA viability parameters. These data suggest that EBDTC rather than Mn may be primarily responsible for the cytotoxicity of organomanganese fungicides on neuronal systems relevant to the pathophysiology of parkinsonism.