Evidence from epidemiological studies and a human intervention trial indicates that selenium (Se) may have chemopreventive activity in humans. This report summarizes a workshop held by the National Cancer Institute to address the use of naturally occurring Se compounds in future cancer chemoprevention trials. Differences in the metabolism of inorganic and organic Se compounds can be seen both in the biochemical handling of these forms and in their kinetics in humans. Long-term supplementation could result in greater increases in muscle stores for organic rather than inorganic forms. Because of long half-lives, trials may have to be of long duration to assess efficacy and safety. The optimal size of dose for supplementation is controversial with respect to both efficacy and safety. In China, selenosis was observed in some individuals with a sustained intake of at least 750 micrograms/day but was not observed among others with intakes exceeding 1 mg. These levels exceed the reference dose, a measure of the maximal safe intake, which is 350 micrograms/day. A large-scale Se human intervention trial in the United States suggests no harm due to long-term Se intake of more than 200 micrograms/day. Se deficiency has been shown to have deleterious effects on the immune system, allowing, for example, a benign form of the Coxsackievirus to become virulent in mice. These recent results may provide an explanation of earlier findings showing a protective effect of elevated Se intakes against a mouse mammary tumor virus. Additional studies on the use of Se as a chemopreventive agent in man seem warranted.