One strain of Salmonella Brandenburg began causing large numbers of human infections in New Zealand in 1998. We investigated the emergence of this strain using combined notification and laboratory data on human and animal disease and a case-control study. S. Brandenburg infection in humans was characterized by spring peaks and high rates in the southern half of the South Island. This epidemic pattern followed very closely that seen in sheep. The case-control study found that infection was significantly associated with occupational contact with sheep and having a household member who had occupational contact with sheep, during the 3 days prior to illness or interview. We conclude that S. Brandenburg has become established as a zoonotic disease in New Zealand. Preventing infection requires control of the epidemic in sheep through vaccination, changes in farm management practices, and promotion of hand washing and other precautions to protect farmers and their families.