AbstractCigarette smoking is a major cause of cancer and lung disease in the U.S. population. The biological processes that underlie the response of the lung to cigarette smoke are important considerations for designing analyses of the effects of occupational exposures. Interactions between cigarette smoking and occupational exposures may occur through a combined effect on the mechanism of disease production, through an effect on the dose of the toxic substances that reach the target issue, or through an effect on the response of the lung to the toxic agents. Disease due to occupational exposures can occur in a similar pattern in both smokers and nonsmokers; however, as more complex interactions are examined, different responses to the same occupational exposure may be identified for smokers and nonsmokers. It is only through the successful intermingling of biologic information with epidemiologic data that these interactions can be fully examined.