SUMMARY An experiment was conducted to determine whether a persistent Salmonella newport infection could be established in swine, to determine duration of shedding and distribution of the organism in internal organs, and to determine whether changes occurred in antimicrobial susceptibility or plasmid profile of the organism during the course of long-term infection. Naturally farrowed Salmonella-free pigs (n = 22) were orally exposed to a multiply antimicrobial-resistant zoonotic strain of S newport when they were 7 weeks old. Tonsillar and rectal swab specimens were examined bacteriologically for S newport during the first week after exposure, then weekly for 7 weeks. Fecal samples were likewise examined weekly or every 2 weeks for 28 weeks after exposure. Necropsies of 2 or 3 randomly selected pigs were conducted at 2, 4, 8, 12, 16, 20, 24, and 28 weeks after exposure. A total of 45 specimens/pig representing the following internal organs or tissues were examined bacteriologically for S newport: liver, spleen, kidney, gallbladder, heart, heart blood, lung, stomach, and tonsils; segments of the intestinal tract with corresponding lymph nodes; and lymph nodes from lymphocenters of the head and neck, thoracic cavity, thoracic limbs, abdominal viscera, and abdominal wall. Exposure to S newport induced a mild and transient clinical response. The organism was recovered from 97% of tonsillar swab specimens and 89% of rectal swab specimens collected during 7 weeks after exposure and from 98% of fecal samples collected during 28 weeks after exposure. At necropsy, S newport was recovered most frequently from tonsils (86.4%), followed by segments of the intestinal tract from ileum to rectum (81.8% recovery from cecal contents), and from mandibular (68.2%), jejunal (50%), and ileocolic (45.5%) lymph nodes. Sporadic recoveries of the organism were made from other lymph nodes and from gallbladder, stomach, kidney, spleen, liver, and heart, varying from 2 to 20 weeks after exposure. The cranial portion of jejunum, medial iliac lymph nodes, dorsal superficial cervical lymph node, and heart blood of all pigs were culture-negative. Of 26 representative isolates of S newport recovered from body organs or feces during 28 weeks after exposure, 4 (15.4%) underwent changes in antimicrobial susceptibility pattern. Changes in plasmid profile of the organism were not detected during longterm infection of swine.