The present study examined the mammary cancer chemopreventive activity of Se-methylselenocysteine, Se-propylselenocysteine and Se-allylselenocysteine in the rat methylnitrosourea (MNU) model. Each compound was supplemented in the diet at a level of 2 ppm Se for the entire duration of the experiment after MNU dosing. Se-Allylselenocysteine was the most active and caused a reduction in total tumor yield by 86%. Se-Methylselenocyteine and Se-propylselenocysteine were similar but less effective, and both produced a decrease of about 50% in tumorigenesis. All three compounds were very well absorbed through the gastrointestinal tract. However, more selenium was excreted in urine after gavaging with Se-propylselenocysteine or Se-allylselenocysteine compared with Se-methylselenocysteine. Analysis of selenium in the mammary gland and other organs showed that tissue selenium levels did not appear to be correlated with differences in chemopreventive activity. A lyase activity capable of catalyzing scission of the Se-alkyl group from the remainder of the amino acid was demonstrated. This activity was found to be high in liver and kidney, but relatively low in mammary gland and intestine. Minimal variations in enzyme activity towards each of the substrates were observed. Our results support the concept that Se-alkylselenoamino acids could be used as precursors for delivering the Se-alkyl moiety and that intrinsic chemical differences in the Se-alkyl substituent of the test compounds are likely to be important determinants of their biological effects.