Previous research has demonstrated that structurally distinctive organoselenium compounds are superior to the corresponding sulfur analogs in cancer prevention. The present study was designed to extend this observation to diallyl selenide (DASe), a volatile synthetic compound, and diallyl sulfide (DAS), a flavor component of garlic. Their anticarcinogenic activities were evaluated using the 7,12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumor model. Rats were gavaged three times with DASe (6 or 12 mumol/kg body wt) or DAS (300, 900 or 1,800 mumol/kg) at 96, 48 and 24 hours before DMBA treatment. Significant tumor inhibition was found with the two doses of DASe and the highest dose of DAS. Based on these results, DASe appears to be at least 300 times more active than DAS. Analysis of total DMBA-DNA binding and individual DNA adducts in the mammary gland and liver showed that DASe had no effect on these parameters, suggesting that DASe might influence some unknown risk-associated events other than carcinogen activation/detoxification. Although the mechanism of action of DASe remains to be elucidated, its potential relevance to natural products will be discussed in the context of the chemistry of selenium-enriched garlic which has been reported to be effective in cancer protection in several studies.