Biocultural medical anthropology connects health outcomes to the local ecology. Much research has examined how culture influences illness beliefs, cognitively held in cultural models which are schematic representations that are widely shared and employed in social life. Consequently, rural/urban differences in the Honduran population may produce distinct cultural models of the illness nervios, a syndrome which shares several similarities with generalized anxiety disorder and major depressive disorder but is not formally recognized in biomedicine. Cultural domain analysis was carried out on a total of n=50 participants in San Pedro Sula and Copán Ruinas to test the hypothesis that Honduran urban participants' cultural model of nervios corresponds more closely to biomedical diagnostic criteria for generalized anxiety disorder and major depressive disorder than that of rural ones. Urban participants were found to name fewer symptoms of nervios overall, but those they did name were more likely to match DSM-IV criteria. Conclusions extend the investigation of cultural syndromes to a previously unstudied region, contribute relevant scholarship regarding the cultural syndrome nervios, expand the investigation of the relationship between illness and culture, and add to relevant discussion in cognitive anthropology concerning how cultural models emerge.