The oxidative metabolism of some exogenous compounds, and possibly some endogenous compounds as well, can lead to the formation of reactive metabolites. These intermediates react as electrophiles, and they lead in some instances to cell death or cell transformation. Three routes (other routes are also known) of toxicity are discussed. These are the epoxide/dihydrodiol pathway, the catechol/o‐quinone pathway, and the alkylation pathway. The possible formation of electrophiles from diethylstilbestrol, from natural estrogens, and from ethynylestradiol is discussed in terms of protein binding. Protein binding is presumptive evidence of electrophile formation, but it does not necessarily indicate that the parent compound is highly cytotoxic, mutagenic, or carcinogenic. Mutagenic and carcinogenic activity is presumed to require reaction of an electrophile with nuclear material. There is evidence for protein binding for these estrogens (diethylstilbestrol, natural estrogens, ethynylestradiol) as a consequence of oxidative metabolism.