Experiments involving 132 weaned piglets were conducted to evaluate the efficacy of a Salmonella enteritidis-immune lymphokine (PILK) derived from the T cells of Salmonella enteritidis (SE)-immunized pigs to protect weaned piglets from Salmonella choleraesuis (SC) infection. Fourteen-to-seventeen day-old piglets were weaned and randomly placed into 1 of 5 groups: (1) noninfected controls, (2) PILK 3X noninfected, (3) SC infected controls, (4) PILK 1X SC infected, and (5) PILK 3X SC infected. PILK was given orally either one time (PILK 1X) or three times (PILK 3X) over 14 days. One hour after the first PILK administration on day 0, piglets were orally challenged with 10(7) cfu of SC. Weights were recorded on day 0, day 7, and day 14. On day 14, pigs in groups 3, 4, and 5 were sacrificed and organs and lymph tissue were cultured for the presence of SC. Three replicates of this experiment were pooled and anlayzed. A significant reduction in the number of pigs positive for SC in the liver, lung, and spleen was found in group 5 (PILK 3X) when compared to group 3 (inf. cont. p < 0.001[). The number of SC positive cecal contents was dramatically reduced in group 5 group when compared to group 3, with the PILK 3X group showing 13% positive pigs versus 55.2% in the infected controls (p < 0.05). Weight gain over the 14 day study in the infected PILK 3X group (group 5) was found to be comparable to the gain observed in the group 1 (noninfected controls). The pigs receiving PILK 3X (group 2) with no SC challenge gained significantly more weight than all other groups, including the noninfected controls (group 1 p < 0.05[). The results of these experiments indicate that PILK protects against SC infection in weaned pigs while enhancing performance in the presence of an SC infection.