Selected members of the genus Astragulus (Fabaceae) are known for their ability to accumulate high levels of selenium, mainly in the form of Se-methyl-selenocysteine. With the aid of cell cultures we have investigated the molecular basis for selenium tolerance of these plants. It is shown that cultured cells from a selenium-accumulating Astragalus species synthesize Se-methyl-selenocysteine in contrast to those of a non-accumulating species and do not unspecifically incorporate selenium into proteins. The purification and biochemical characterization of a selenocysteine methyltransferase from cultured Astragalus bisculatus cells is described, which does not accept cysteine as a substrate. We propose that this enzyme plays a crucial role in conferring selenium tolerance.