The working group on tropospheric ozone of the Health Effects Institute has evaluated the need for epidemiologic studies on the health effects of ozone (O3) exposure. This paper summarizes current data and identifies possible research questions. The extent to which ozone exposure results in chronic health effects is largely undefined and is the central issue for epidemiologic studies. Most current data focus on transient endpoints; the link between acute changes in symptoms and/or lung function and possible chronic effects has not been established. Concepts of ozone-induced health effects have been extended to include processes of chronic disease (e.g., markers of ongoing inflammation and repair, markers of accelerated lung aging). Traditional epidemiologic studies performed have focused only on accelerated lung aging and are limited by a number of methodologic problems. Recent, very preliminary, studies suggest new opportunities for the use of human lung tissue and a variety biological response markers as part of epidemiologic studies. The identification of sensitive subpopulations with regard to ozone-induced health effects has been studied incompletely and is important both in terms of study efficiency and mechanistic insight. Methodologic advances in the reconstruction of past ozone exposure are seen as essential, as is the incorporation of emerging markers of biologic response to ozone into traditional epidemiologic study designs. Finally, more data on the joint and independent contribution of other ambient air pollutants to putative ozone-induced health effects is warranted.