A large number of halogenated phenols are detected in the blood of humans, fish and wild-animals. We have characterized the estrogen-like activity of phenol, 4-bromophenol (4-BP), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and 4-tert-butylphenol (tert-BP) using the estrogen-dependent human breast cancer cell line MCF-7. 4-BP, 2,4-DBP and 4-tert-BP all bind to the estrogen receptor (ER) with approximately 10,000-fold less affinity than 17 beta-estradiol (17 beta-E). 2,4,6-TBP was only able to displace 43% of radiolabelled estrogen when tested at concentrations up to 1 microM, whereas phenol had no affinity for the ER. 4-tert-BP stimulated cell growth and induced estrogen-regulated proteins such as the progesterone receptor (PgR) and pS2. The brominated phenols, however, although binding to the ER, did not stimulate cell growth or increase the levels of the PgR or pS2, or reduce the level of 17 beta-E induced pS2. On the contrary, 4-BP, 2,4-DBP and partly 4-tert-BP reduced 17 beta-E-stimulated cell growth apparently by an ER independent mechanism.