Pre- and post-immunization serum antibodies to pneumococcal polysaccharides (PPS) and tetanus toxoid (TT) were measured in 25 patients with persistent generalized lymphadenopathy and serum antibodies to the human immunodeficiency virus (HIV). The increase in post-immunization anti-PPS antibodies was lower than 40% in 16/25 patients. Isotype analysis indicated that the IgM, IgA, IgG2, but not the IgG1 antibody responses were lower in patients that in healthy controls, whereas pre-immunization values were similar. For TT, no difference was found between the patients and the healthy group in total and IgG1 antibody response whereas IgG4 response was lower in patients. No significant association was found between the defect in anti-PPS antibody response and associated thrush or constitutional symptoms or other immunological parameters. These findings suggest that defective response to a thymo-independent polysaccharide antigen is a distinctive consequence of HIV infection.