Chronic exposure to excess level of arsenic through contaminated drinking water is associated with many injuries, among which skin lesions are the most prominent. In this study, we measured the concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in the blood of the residents of arsenicosis area, who demonstrated different skin lesion grade from mild, moderate to advanced. We evaluated the individual methylation capacity by two indices of the first and secondary methylation ratio (FMR and SMR). We found that SMR of moderate and advanced groups were markedly lower than that of mild group. Significant negative correlation was found between SMR of all the subjects and the grade of skin lesion, with Spearman's correlation coefficient of −0.429 (P = 0.016). Moreover, blood MMA proportion of moderate and advanced groups was found to be significantly higher than that of the mild group. These results suggest that low secondary arsenic methylation capacity and high MMA proportion are associated with the severity of arsenic-related skin lesions. Our findings evaluated by blood speciation is consistent with that evaluated by the generally accepted urinary arsenic speciation in the relationship between arsenic methylation capacity and arsenic-related lesions. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 118–123, 2011.