The development of new compounds with greater cancer inhibitory activity and that are well tolerated continues to be a priority in chemoprevention research involving selenium. One compound, 1,-4-phenylene-bis(methylene)selenocyanate (p-XSC), is representative of a series of organoselenium compounds with these characteristics. In this study, the effects of p-XSC on a mouse mammary carcinoma cell line were compared to those of sodium selenite, which has been shown to be growth inhibitory. Treatment with p-XSC caused a 3- to 6-fold greater accumulation of selenium within cells than did treatment with equivalent amounts of selenite and cells were able to better tolerate higher cellular levels of selenium derived from p-XSC. Both compounds resulted in a dose-dependent reduction in cell number after 24 h of exposure. Selenite and p-XSC also caused a dose-dependent increase in cell death by apoptosis. This effect was observed within 5 h of treatment. The effect of p-XSC on apoptosis was more pronounced than that of selenite, especially at the 20 microM level of exposure. The induction of apoptosis by selenium compounds may partially account for their chemopreventive activity.