Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitively established. Specific preparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available cross-protective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pools.