Humoral immune responses and protective efficacy by various doses of Salmonella ghost cells carrying enterotoxigenic Escherichia coli (ETEC) fimbrial antigens for protection against piglet colibacillosis were studied. All groups were orally primed and boosted at 11 and 14 wk of pregnancy, respectively. Group A sows were inoculated with phosphate-buffered saline (PBS), and groups B, C, and D sows were immunized with 2 × 10(9) 2 × 10(10), and 2 × 10(11) ghost cells, respectively. Serum immunoglobulin (Ig)G, and colostrum (Ig)G and (Ig)A levels of groups C and D sows were significantly higher than those of group A sows. In addition, serum (Ig)G and (Ig)A levels in group C and D piglets were significantly increased compared to those of group A piglets. After challenge with wild-type ETEC, diarrhea and mortality were not observed in group C and D piglets, while diarrhea was observed in 88.9% and 58.8% of groups A and B piglets, respectively, and 16.7% mortality was observed in group A piglets. These findings indicate that oral immunization of sows with 2 × 1010 or 1011 ghost cells can effectively protect their offspring from colibacillosis.