This experiment was designed to study the natural transmission of Salmonella choleraesuis in swine. Forty pigs were divided into three groups. Group 1 (n = 12) was challenged with 10(8) CFU of S. choleraesuis per ml by intranasal inoculation. One day postinoculation (p.i.), group 2 (n = 24) was commingled with group 1. Group 3 (n = 4) served as uninoculated controls. Serum samples were collected weekly. Blastogenesis assays and necropsies were performed at 1, 2, 4, 6, 9, and 12 weeks p.i., and 16 tissue samples per pig were collected and cultured. Environmental (pooled feces from the pen floor) levels of S. choleraesuis were 2.61 log10 CFU/g of feces at 24 h p.i. (immediately prior to commingling). Severe clinical signs were observed in groups 1 and 2. The results indicated that at least 16% of group 2 pigs were shedding S. choleraesuis within 24 h of commingling. At 1 week p.i., 32 of 32 group 1 and 39 of 62 group 2 tissue samples were positive for S. choleraesuis. Only 3 of 12 group 2 pigs were positive at 6, 9, and 12 weeks (1 pig for each week), indicating that only a small proportion of infected swine become long-term carriers. At 12 weeks p.i., only the colon and colonic lymph node samples of one pig from group 2 were positive. Humoral, mucosal, and cellular immune responses were similar between groups 1 and 2. These data demonstrate that a few pigs shedding low levels of Salmonella organisms before slaughter can result in rapid transmission and subsequent shedding by many swine.