Antibody response to an Haemophilus influenzae type b (Hib)-conjugated vaccine was studied in 59 healthy adults (mean age: 32 yr) and 22 patients with humoral immunodeficiencies (mean age: 32 yr) to determine its usefulness in the diagnosis of defective antibody formation. Twenty of the healthy adults and nine of the patients were also immunized with a pneumococcal vaccine. Serum specific antibodies were measured by ELISA. Adequate response to both vaccines was defined using the lower limit of the two-tailed 90% probability interval of postimmunization specific IgG of the healthy adults. By using this cutoff, responders were considered to be those with an absolute increase in anti-Hib IgG titers higher than 2.28 microgram/ml, and in anti-Streptococcus pneumoniae IgG higher than 395 arbitrary units/ml. With these criteria, 85% (50 of 59) of the healthy adults responded with anti-Hib IgG and 75% (15 of 20) with anti-pneumococcal IgG. All healthy adults receiving both vaccines responded to at least one. None of the patients with humoral immunodeficiencies responded to either vaccine. Evaluation of the antibody response to both the Hib and pneumococcal vaccines may facilitate the diagnosis of humoral immunodeficiency and selection of patients to receive immunoglobulin therapy.