To study the effects of inorganic arsenicals on the methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells.The methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells were measured by methylation-specific PCR (MSP) and RT-PCR methods.(1) The exposure of the BEP2D cells to sodium arsenite (0.016 approximately 2 micromol/L) or high-density sodium arsenate (80 approximately 160 micromol/L), but not low-density sodium arsenate (20 approximately 40 micromol/L), produced significant hypermethylation of p16 gene CpG islands in BEP2D cells. (2) The expressions of p16 gene in the groups of sodium arsenite and sodium arsenate at the test were lower than that of the control group, especially in the groups of sodium arsenite.Inorganic arsenicals alter the methylation patterns and the expression of p16 gene in BEP2D cells, which suggests that the hypermethylation of p16 gene CpG islands may be one of the mechanisms of carcinogenesis of inorganic arsenicals.