We studied the role of S-adenosylmethionine (SAM) as a methyl group donor in the methylation of inorganic arsenic in mammalians. The SAM and S-adenosylhomocysteine (SAH) levels in the livers of untreated hamsters were 74.3 +/- 8.2 and 40.0 +/- 6.4 nmol/g, respectively. The SAM level was 63.9 +/- 6.5 nmol/g following oral administration of 1.5 mg/kg of arsenic trioxide, which was 14% lower than the control level (t-test, p less than 0.05). This fall of the SAM level in the liver presumably derived from the SAM having acted as a methyl group donor. Oral administration of 1.5 mg/kg of arsenic trioxide once only to hamsters pretreated intraperitoneally with 2.0 mg/kg of SAM once only gave the following arsenic levels in the liver and urine. The dimethylated arsenic (DMA) levels in the livers of hamsters treated with SAM plus arsenic trioxide were significantly high, that is, 2 times as high as the control value at 6 hours, and 1.5 times as high as the control value at 24 hours after the administration of arsenic trioxide. The urinary DMA excretion rate was significantly higher, that is, higher by 36%, than the control value. The urinary DMA excretion rate following pretreatment with SAM was not dose-dependent. Pretreatment with methionine failed to exert any significant acceleratory effect on the methylation of arsenic trioxide. The decreasing pattern of the SAM level in the liver following administration of arsenic trioxide and the DMA behavior in the liver and urine following administration of SAM and arsenic trioxide revealed that SAM accelerated the methylation of inorganic arsenic. In other words, it appeared that SAM could be a very potent methyl group donor to inorganic arsenic.