In one of the earliest extensive animal models of smallpox, Brinckerhoff and Tyzzer (1906) reported the effect of inoculating cynomologus monkeys with variola at different sites. Inoculation of mucus membranes of the lip, palate, and nose produced local lesions, but generalized rash occurred in only 10% of animals. Inoculation through the skin produced a local lesion and a generalized eruption in 70-80% of animals. Animals inoculated by scratching the tracheal mucosa through a rigid bronchoscope all developed a generalized rash, and one developed a variolous bronchitis and pneumonia. Laryngeal instillation of dry pustule contents produced infections while instillation of powdered crusts did not. Inhalation exposures to an atomizer spray of vesicle contents infected only one of five monkeys; however, the particle size distribution and type of atomizer were not reported.