The Mont Blanc Tunnel disaster in March 1999 intensified the debate over international road freight transport in the Alpine valleys. Air pollution caused by road traffic is among the nuisances cited, and residents are legitimately concerned about its health consequences. The InVS asked the Rhône-Alpes-Auvergne Regional Health Agency to study the relevance and feasibility of research aimed at assessing these consequences. The closure of the Mont Blanc Tunnel, the halting of cross-border traffic in the Chamonix Valley (Arve Valley), and its diversion to the Fréjus Tunnel at the end of the Maurienne Valley can be summarized, in terms of air pollution, by this two-part question: Have changes in emissions occurred, and has this had consequences for public health? This question was examined from two angles: i) the relevance of conducting epidemiological studies to aid decision-making in the context of transalpine road transport; ii) the feasibility of such studies. A technical context conducive to selecting a time-series ecological study protocol, as well as to developing sensitive health indicators based on medication consumption data collected by the National Health Insurance Fund (CNAMTS), guided the planning for an epidemiological study. Conducting a health impact assessment was also considered. A review of the scientific literature on studies conducted to assess the specific impact of road traffic air emissions, along with a description of the indicators available in the Arve and Maurienne valleys regarding exposure, medication use, and certain co-factors, appears to support the feasibility of conducting a time-series study. Conducting a health impact assessment is not feasible if the goal is to work with an indicator whose sensitivity would lend the results demonstrative power in areas with a small population: there is, in fact, no exposure-risk relationship linking traffic intensity to the incidence rate of medical prescriptions. The relevance of conducting an epidemiological study lies primarily at the scientific level, in the effort to establish exposure-risk relationships between road traffic indicators—considered representative of exposure to this specific source of air pollution—and indicators of medication use.