Sodium selenite, sodium selenate, selenium oxide, selenophypoxanthine, selenopurine, selenocysteine, selenoethionine and selenomethionine were tested for their ability to induce endogenous retrovirus expression in cultured AKR mouse embryo fibroblasts. All except selenoethionine were highly toxic to the cells. Only selenomethionine however, had the ability to induce virus expression under the conditions used. The level of virus induction (plaque-forming-units/10(5) cells) was roughly proportional to dose over the range of concentrations from 0.25 mM to 5.0 mM. Induction was best observed when a treatment duration of 48 h was used and required the treatment of actively dividing cells. The induction and the cytotoxic effects of selenomethionine could be abrogated by simultaneous treatment with methionine. A ratio of methionine to selenomethionine of 1:10 inhibited induction by approx. 60% while equivalent amounts of methionine inhibited selenomethionine-mediated induction by greater than 96%, indicating that methionine was more efficiently recognized by the cells than was selenomethionine. A possible mechanism for selenomethionine induction involving the production of undermethylated DNA is presented.