Some DDT analogs are estrogenic, particularly o,p'-DDT, which comprises approximately 15-20% of the commercial DDT mixture. Whether this compound or its metabolites are active has not been established. In fact, the data obtained thus far are more confusing than enlightening. For example, CCl4 pretreatment of immature female rats has been reported to inhibit or enhance estrogenic activity of o,p'-DDT, and SKF-525A pretreatment has been reported to enhance or not alter the estrogenic effect. Although o,p'-DDT inhibits binding of estradiol to the estrogen receptor from rat or human at low levels (approximately 1-10 micrometer) in vitro, higher levels are required to inhibit nuclear binding of [3H] estradiol in incubated whole uteri. Futhermore, o,p'-DDT appears to be neither estrogenic nor antiestrogenic in an in vitro estrogen assay. Methoxychlor appears to be "activated" by metabolism, and it is probable that phenolic metabolites are responsible for its estrogenic activity. Since chlorinated hydrocarbons often enhance the metabolism of steroids and may reduce circulating levels of steroids, interactions of the exogenous hormonally active agents with steroid receptors may be self-potentiating in vivo.