Data from nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results Program (1973-1982) were analyzed to determine whether the incidence of different histologic types of respiratory tract cancers varies by anatomic location. The variation in cancer incidence among respiratory tract subsites was remarkable for squamous cell carcinoma, but the variation was less prominent for adenocarcinoma. The rates of squamous cell carcinoma and adenocarcinoma along the airways correspond closely with the deposition pattern of large and small smoke particles, respectively. Also, the rates of adenocarcinoma parallel the distribution of surface glandular cells of the respiratory tract. Our results support the hypothesis that anatomy and physiology, in conjunction with size of particles in inhaled cigarette smoke, play an important role in the genesis of specific histologic types of respiratory tract cancers.