We compare physicians and laypeople within and across cultures, focusing on similarities and differences across samples, to determine whether cultural differences or lay–professional differences have a greater effect on explanatory models of the common cold. Data on explanatory models for the common cold were collected from physicians and laypeople in South Texas and Guadalajara, Mexico. Structured interview materials were developed on the basis of open-ended interviews with samples of lay informants at each locale. A structured questionnaire was used to collect information from each sample on causes, symptoms, and treatments for the common cold. Consensus analysis was used to estimate the cultural beliefs for each sample. Instead of systematic differences between samples based on nationality or level of professional training, all four samples largely shared a single-explanatory model of the common cold, with some differences on subthemes, such as the role of hot and cold forces in the etiology of the common cold. An evaluation of our findings indicates that, although there has been conjecture about whether cultural or lay–professional differences are of greater importance in understanding variation in explanatory models of disease and illness, systematic data collected on community and professional beliefs indicate that such differences may be a function of the specific illness. Further generalizations about lay–professional differences need to be based on detailed data for a variety of illnesses, to discern patterns that may be present. Finally, a systematic approach indicates that agreement across individual explanatory models is sufficient to allow for a community-level explanatory model of the common cold.