There is a worldwide epidemic of chronic obstructive pulmonary disease (COPD) in women. Some large epidemiologic studies suggest that female smokers may have increased susceptibility to COPD. The biological mechanisms to explain these observations are far from certain. However, the susceptibility to the effects of cigarette smoke in women could be due to a greater deposition of toxic substances in the lung, impaired clearance of the toxins that are deposited, and/or an exaggerated biologic response to these toxins. The latter effect could be due to an increased ability to convert certain xenobiotics to more toxic metabolites or to a decreased ability to conjugate and excrete metabolites of these toxins. Female hormones, in particular estrogen, can up-regulate certain cytochrome P450 enzymes without altering detoxifying enzymes, leading to a disturbance in the balance between metabolism and conjugation. This article reviews this and other potential mechanisms that may confer increased susceptibility of COPD to female smokers.