Was vaccination the only cause of the decline of smallpox in Norway during the 19th century? This regional study focuses on the history of the disease in Telemark county with special emphasis on the last, extensive epidemic in 1868. In addition to vaccination, other possible causal relations are discussed. In Telemark, smallpox seems to have been relatively mild in the 19th century with the exception of the epidemics at the end of the 1830s and in 1868. In 1868 the disease spread along the main transportation routes northward through the western part and eastward through the more densely populated districts along the coast. The importance of vaccination is apparent from the fact that the municipalities with the lowest annual percentage of newborns vaccinated were most heavily struck by the epidemic. Despite vaccination procedures, both adults and unvaccinated children were groups at risk. Local initiatives--especially isolation and revaccination--largely prevented or restricted outbreaks of smallpox. It seems that the efforts of the district medical officers and local health administrators after 1860 were of decisive importance for the decline in smallpox cases in the period in question.