Previously, protoberberine alkaloids such as berberine and palmatine have been found to lower dopamine content in PC12 cells (Shin et at., 2000). In this study, the effects of berberine and palmatine on L-DOPA-induced increase in dopamine level and cytotoxicity in PC12 cells were investigated. Treatment of PC12 with L-DOPA at concentration ranges of 20∼50 $mu$M increased dopamine content and the increase in dopamine levels by L-DOPA was inhibited by 10∼40 $mu$M berberine and 10∼80 $mu$M palmatine, which the concentration ranges did not show a cytotoxicity. However, berberine and palmatine at concentrations higher than 50 $mu$M and 100 $mu$M caused a cytotoxicity, respectively. In addition, berberine (10∼20 $mu$M) and palmatine (10∼50 $mu$M) at non-cytotoxic concentration ranges aggravated L-DOPA-induced cytotoxicity in PC12 cells (L-DOPA concentration ranges, 20∼50 $mu$M). The L-DOPA-induced cytotoxicity was also significantly potentiated by berberine (50 $mu$M) and palmatine (100 $mu$M) with cytotoxic ranges. These data demonstrate that berberine and palmatine inhibit L-DOPA-induced increase in dopamine content and stimulate L-DOPA-induced neurotoxicity. Therefore, the possibility that the long-term L-DOPA treated patients with berberine and palmatine could be checked the adverse symptoms.