Nitrogen dioxide (NO2) is an oxidant gas which contaminates ambient air in many urban and industrial locations, and indoor air in homes with combustion appliances. The Environmental Protection Agency presently regulates NO2 in ambient air as a "criteria" pollutant. In spite of decades of laboratory, clinical, and epidemiological research, the health effects of NO2 exposure on humans are not well understood. The toxicological evidence suggests that increased susceptibility to infection, functional deficits from effects on airways, and deterioration of the status of persons with chronic respiratory conditions, including asthmatics, are of potential concern. This paper provides a perspective on the present evidence related to human health effects of NO2. It addresses methodological barriers that limit the available data; assesses the adequacy of the data for risk assessment; and proposes a research agenda to obtain needed information on the health effects of NO2.