OBJECTIVE: Recent clinical studies have shown that arsenic trioxide (As_2O_3) at low concentrations induces a complete remission with minimal toxicity in patients with refractory acute promyelocytic leukemia (APL). Studies suggest that As_2O_3 induces apoptosis and possible differentiation in APL cells. Like APL cells, neuroblastoma (NB) cells are thought to be arrested at an early stage of differentiation, and cells of highly malignant tumors fail to undergo spontaneous maturation. This study was designed to investigate the effect of (As_2O_3) on apoptosis of neuroblastoma cells in vitro and its mechanism. METHODS: The effect of a wide range of concentrations of As_2O_3 on the proliferation of neuroblastoma cells was measured by the colorimetric method. Morphological changes of the cells were observed under the optical microscope in Giemsa stain. Cell apoptosis was determined by the flow cytometry assay in Annexinⅴ/PI stain. Bcl-2 was detected by the immunocytochemical method. RESULTS: 0.5- 4.0 μmol/L As_2O_3 significantly inhibited the proliferation of the neuroblastoma cell line SK-N-SH and the inhibitory effect was dose- and time-dependent, which was accompanied by the appearance of morphologic characteristics of apoptosis. After 4.0 μmol/L As_2O_3 treatment for 72 hrs, the percentage of apoptotic cells [(9.9±0.8)%] increased significantly when compared with the untreated controls [(3.7±0.2)%] (P<0.05). The expression level of bcl-2 was down-regulated as the concentration of As_2O_3 increased. SK-N-SH cells treated with 1.0 μmol/L, 2.0 μmol/L, and 4.0 μmol/L As_2O_3, the percentage of bcl-2 positive cells [( 26.3±8.0)%, (15.0±4.5)% and (4.8±3.2)% respectively] decreased significantly when compared with the untreated controls [(73.6±6.1)%] (P<0.01). CONCLUSIONS: As_2O_3 may inhibit the proliferation and induce apoptosis of the neuroblastoma cells, in which bcl-2 is involved.