The effects of tributyltin acetate (TBTA) on dopamine biosynthesis and L-3,4-dihydroxypheny-lalanine (L-DOPA)-induced cytotoxicity in PC12 cells were examined. TBTA at concentrations of 0.1-0.2 ${mu}M$ inhibited dopamine biosynthesis by reducing tyrosine hydroxylase (TH) activity and TH gene expression in PC12 cells. TBTA at 0.1-0.4 ${mu}M$ also reduced L-DOPA (20-50 ${mu}M$)-induced increases in dopamine content for 24 h in PC12 cells. TBTA at concentrations up to 0.3 ${mu}M$ did not affect cell viability. However, TBTA at concentrations higher than 0.4 ${mu}M$ caused apoptotic cytotoxicity. Exposure of PC12 cells to non-cytotoxic (0.1 and 0.2 ${mu}M$) or cytotoxic (0.4 ${mu}M$) concentrations of TBTA with L-DOPA (20, 50 and 100 ${mu}M$) significantly increased the cell loss and the percentage of apoptotic cells after 24 or 48 h compared with TBTA or L-DOPA alone. These data suggest that TBTA inhibits dopamine biosynthesis and enhances L-DOPA-induced cytotoxicity in PC12 cells.