As a first step in exploring the feasibility of passive antibody prophylaxis and therapy of serious infections caused by common encapsulated bacteria, we have immunized healthy adults with Haemophilus influenzae type b vaccine, 14-valent pneumococcal vaccine, and meningococcal group A and C vaccine; collected plasma by repeated pheresis; and purified a hyperimmune globulin termed bacterial polysaccharide immune globulin by the cold-ethanol fractionation method of Cohn and Oncley. Specific antibacterial antibody concentrations were measured in individual donors before and after immunization. In addition, antibody concentrations were measured in plasma pools prepared from immunized donors and from unimmunized controls and in the immunoglobulin-containing Cohn-Oncley fractions II and III derived from the respective plasma pools. A comparison of Cohn-Oncley fractions II, which contain primarily immunoglobulin G and which are used therapeutically as immune globulin, revealed that antibody to H. influenzae type b was enriched 15.3-fold and that antibody to meningococcal serogroups and pneumococcal types was enriched a mean of 4.4-fold (range, 1.2- to 9.9-fold). Enrichment of antibacterial antibody in Cohn fraction III, which contains substantial amounts of immunoglobulin M and immunoglobulin A in addition to immunoglobulin G, closely paralleled that in fraction II. Only antibodies to pneumococcal types 1 and 7 were increased disproportionately in fraction III. Based on the clinical experience that conventional immune serum globulin at a dose of 100 mg/kg protects agammaglobulinemic patients for ca. 1 month, we estimate that bacterial polysaccharide immune globulin, in similar dosage, will provide protection from systemic H. influenzae type b infection for 4 to 6 months and from pneumococcal and meningococcal infections for 3 to 4 months.