A prospective study of antibody production by adults infected with human immunodeficiency virus (HIV) after vaccination with tetanus toxoid-conjugated Haemophilus influenzae type b (Hib) vaccine was conducted. Concentrations of antibodies to the two immunogenic components of the vaccine (i.e., polyribosylribitolphosphate [PRP] and tetanus toxin) were determined. Individuals were divided into three groups according to the CD4+ T lymphocyte count: group 1, < or =100 x 10(6)/L; group 2, 101-300 x 10(6)/L; and group 3, >300 x 10(6)/L. After vaccination, concentrations of IgM and IgG antibodies to PRP were significantly lower in group 1 than in the other patient groups and controls. A CD4+ T lymphocyte count of <100 x 10(6)/L and an impaired proliferative response of lymphocytes to monoclonal antibody to CD3 were independently associated with a less than threefold increase in concentrations of IgG antibody to PRP. Analysis of IgG subclasses demonstrated that the production of IgG1 antibodies was predominantly affected. Postvaccination concentrations of antibody to tetanus toxin were significantly lower in group 1 than in group 3 and controls. Both prevaccination and postvaccination concentrations of antibody to tetanus toxin were not correlated with the magnitude of the response of antibody to PRP. We conclude that HIV-infected individuals with CD4+ T Iymphocyte counts of <100 x 10(6)/L demonstrate an impaired antibody response after vaccination with conjugated Hib vaccine.