75Se-labeled selenite was used to study its metabolism by intact rat erythrocytes in vitro. Utilizing both N-ethylmaleimide and excess selenite to lower erythrocyte GSH concentrations it was shown that the uptake and subsequent metabolism of selenite was dependent upon GSH. The secondary release of Se by rat erythrocytes had no relation to the erythrocyte transport of GSSG. While fluoride depressed and chromate increased GSSG transport, chromate, a glutathione reductase inhibitor, decreased Se release. This was consistent with the concept that the release was secondary to a reaction catalyzed by gluthathione reductase. The similarity of the I50 values for chromates' irreversible inhibition of glutathione reductase and for the inhibition of Se release further suggested a relationship between these two events. These results supported the hypothesis that H2Se or a similar product of GSSeSG reduction by glutathione reductase was the final product of selenite metabolism by rat erythrocytes.