A rice cDNA, OsDEP1, encoding a highly cysteine (Cys)-rich G protein γ subunit, was initially identified as it conferred cadmium (Cd) tolerance on yeast cells. Of the 426 aa constituting OsDEP1, 120 are Cys residues (28.2%), of which 88 are clustered in the C-terminal half region (aa 170–426). To evaluate the independent effects of these two regions, two truncated versions of the OsDEP1-expressing plasmids pOsDEP1(1–169) and pOsDEP1(170–426) were used to examine their effects on yeast Cd tolerance. Although OsDEP1(170–426) conferred a similar level of Cd tolerance as the intact OsDEP1, OsDEP1(1–169) provided no such tolerance, indicating that the tolerance effect is localized to the aa 170–426 C-terminal peptide region. The Cd responses of transgenic Arabidopsis plants constitutively expressing OsDEP1, OsDEP1(1–169) or OsDEP1(170–426), were similar to the observations in yeast cells, with OsDEP1 and OsDEP1(170–426) transgenic plants displaying Cd tolerance but OsDEP1(1–169) plants showing no such tolerance. In addition, a positive correlation between the transcript levels of OsDEP1 or OsDEP1(170–426) in the transgenics and the Cd content of these plants upon Cd application was observed. As several Arabidopsis loss-of-function heterotrimeric G protein β and γ subunit gene mutants did not show differences in their Cd sensitivity compared with wild-type plants, we propose that the Cys-rich region of OsDEP1 may function directly as a trap for Cd ions.