Antibodies against common gram-negative core antigens can provide protection against environmental, commensual, and contagious bacteria that cause life-threatening gram-negative sepsis/endotoxemia. Cross-protective immunity may be effective against many common livestock diseases, including neonatal coliform septicemia, coliform mastitis, septic metritis, and severe enteritis. The greatest potential benefit of cross-protective immunity may be realized in the reduction of ill-thrift and mortality of neonates. The use of active and passive immunization against core antigens common to gram-negative bacteria has been successful in human beings, laboratory animals, and livestock. Protection has been observed following challenge with either heterologous endotoxin or unrelated, live, virulent gram-negative bacteria.