text: We reported previously that garlic cultivated with selenite fertilization showed powerful chemopreventive activity in the rat dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model (Carcinogenesis 15, 573-576, 1994). In order to ascertain that the efficacy of the high-selenium garlic in cancer protection is primarily dependent on the action of selenium we compared the effects of two batches of garlic powder with marked differences in their level of selenium enrichment, 112 or 1355 p.p.m. Se dry weight. Both products were added to the diet to achieve the same final concentration of 2 p.p.m. Se. The supplementation protocol was designed to evaluate the efficacy during either the initiation phase or post-initiation phase of DMBA mammary carcinogenesis. Significant tumor reduction was observed with either treatment protocol. Furthermore, the magnitude tumor suppression, as well as the extent of DMBA-DNA adduct inhibition, were very similar with the two batches of garlic, even though the amounts of garlic in the diet varied considerably between them (1.8% for the 112 p.p.m. Se garlic versus 0.15% for the 1355 p.p.m. Se garlic). This suggests that the anti-cancer activity of the high-selenium garlic was likely to be accounted for by the effect of selenium, rather than the effect of garlic per se. A continuous feeding of the high-selenium garlic produced a modest increase in total selenium in various tissues. In general the profile of selenium accumulation was comparable in rats ingesting either the 112 or the 1355 p.p.m. Se garlic. Thus, based on the results of several biological responses, it appears that the ability of the high-selenium garlic to protect against tumorigenesis is primarily dependent on increased intake of selenium provided by the vegetable. Future research will be focused on the chemical form of selenium in the garlic.