In December 1801, the first vaccination against smallpox in Norway took place. Vaccine material came from Denmark, England, Ireland, and other countries; it was also obtained from a few local cowpox cases. What mattered was the effect, not the origin. Several reports indicate that variola virus itself, the cause of smallpox, was also used for human vaccination after passages through cows and horses. A vaccine institute for production of vaccine in calves was established in Kristiania in 1891. Cowpox was once a rare disease in cattle, but a total of 70,985 bovine cases were reported between 1889 and 1928. The source of infection was thought to be humans vaccinated against smallpox. Pox-like diseases were also registered in horses, pigs, sheep, goats and dogs at that time. Compulsory vaccination continued in Norway until 1976; smallpox is now eradicated. During the last decades, however, cowpox virus infections have re-emerged among zoo animals, domestic cats and humans in Western Europe, with small wild rodents and shrews as wildlife reservoirs. Vaccinia virus is also met with new interest as a vector in recombinant vaccines. Given the fact that the human population no longer has immunity against orthopoxviruses and the new possible exposure through pets and wildlife, it may be appropriate to reflect on poxvirus history in Norway in the light of the present situation.