Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.