Humic substances in groundwater and aquifer sediments from the arsenicosis and Blackfoot disease (BFD) affected areas in Bangladesh (Bengal delta plain) and Taiwan (Lanyang plain and Chianan plain) were characterized using fluorescence spectrophotometry and Fourier transform infrared (FT-IR) spectroscopy. The results demonstrate that the mean concentration of As and relative intensity of fluorescent humic substances are higher in the Chianan plain groundwater than those in the Lanyang plain and Bengal delta plain groundwater. The mean As concentrations in Bengal delta plain, Chianan plain, and Lanyang plain are 50.65 μg/l (2.8-170.8 μg/l, n=20), 393 μg/l (9-704 μg/l, n=5), and 104.5 μg/l (2.51-543 μg/l, n = 6), respectively. Average concentrations and relative fluorescent intensity of humic substances in groundwater are 25.381 QSU (quinine standard unit) and 17.78 in the Bengal delta plain, 184.032 QSU and 128.41 in the Chianan plain, and 77.56 QSU and 53.43 in the Lanyang plain. Moreover, FT-IR analysis shows that the humic substances extracted from the Chianan plain groundwater contain phenolic, alkanes, aromatic ring and amine groups, which tend to form metal carbon bonds with As and other trace elements. By contrast, the spectra show that humic substances are largely absent from sediments and groundwater in the Bengal delta plain and Lanyang plain. The data suggest that the reductive dissolution of As-adsorbed Mn oxyhydroxides is the most probable mechanism for mobilization of As in the Bengal delta plain. However, in the Chianan plain and Lanyang plain, microbially mediated reductive dissolution of As-adsorbed amorphous/crystalline Fe oxyhydroxides in organic-rich sediments is the primary mechanism for releasing As to groundwater. High levels of As and humic substances possibly play a critical role in causing the unique BFD in the Chianan plain of SW Taiwan.