Bone marrow transplant patients have impaired responses to pure polysaccharide (PS) vaccines and are at an increased risk for disease caused by PS encapsulated pathogens such as Haemophilus influenzae type B (HIB) and Streptococcus pneumoniae. We immunized 35 BMT patients (21 allogeneic and 14 autologous) ages 2-45 years with pure PS pneumococcal (Pnu-imune 23) HIB-conjugate (HibTITER), and tetanus toxoid vaccines. Patients were assigned to receive vaccines at either 12 and 24 months after transplantation or at 24 months only. Only 19% of all enrolled patients developed protective antibody concentrations (> or = 0.300 microgram antibody nitrogen/ml) to the 6 pneumococcal serotypes measured after the 24-month immunization. Poor response to pneumococcal vaccine was not different for the 2 study groups and was similar to previous studies. In contrast, HIB-conjugate vaccine elicited protective concentrations of antibody (> or = 1.0 microgram/ml) in 56% of patients after 1 dose and in 80% after 2 doses. The group that received 2 doses of HIB-conjugate vaccine had a significantly higher geometric mean antibody concentration of 14.5 micrograms/ml as compared with 1.43 micrograms/ml for those receiving only 1 dose (P = 0.012). Responses to tetanus toxoid vaccine were similar to HIB-conjugate vaccine, with a booster response documented after the second dose. In summary, 2 doses of HIB-conjugate vaccine given at 12 and 24 months after transplantation produced protective antibody concentrations in 80% of patients. While the response to pure PS pneumococcal vaccine was poor, the results with HIB-conjugate vaccine suggest that future pneumococcal conjugate vaccines may also benefit BMT patients.