Environmental exposures to very low levels of airborne chemicals are associated with adverse symptoms, often affecting multiple organ systems, in the phenomenon of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of chemically sensitive subjects in the United States, but the mechanism linking exposure to symptoms remains unclear, despite the advancement of a variety of theoretical models. In many of these models, exposure of the nasal respiratory system to an airborne agent is the first step in the pathway leading to symptoms. In this article, we advance the hypothesis that interactions between environmental chemicals and the vomeronasal organ (VNO) may play a role in the etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves in animals as part of a sensitive chemosensory system; however, evidence suggesting that the VNO retains a functional role in the adult human is controversial. Reported characteristics of the human VNO relevant to CS, including location, prevalence, selective sensitivity to airborne chemical exposure, and capacity to produce systemic effects, are discussed within the context of this ongoing debate. Beyond relevance to CS, the demonstration of an active, adult VNO could have significant impact on environmental toxicology.