We measured serum anti-pneumolysin IgG concentrations in a prospective cohort of 34 HIV infected adults who developed recurrent pneumococcal bacteraemia, and compared baseline levels with HIV positive and HIV negative control subjects that remained free of pneumococcal disease. Anti-pneumolysin concentrations in HIV positive cases and controls were higher compared to HIV negative controls. There was no significant difference in levels between HIV positive subjects who did and did not subsequently develop pneumococcal bacteraemia (geometric means 849.1 U/ml vs. 564.6 U/ml, p=0.059). Anti-pneumolysin IgG titres before, and after the recurrent episode of pneumococcal bacteraemia did not differ significantly (p=0.95). High levels of anti-pneumolysin IgG do not predict protection from invasive pneumococcal disease or indicate that an effective immune response has occurred in HIV infected patients.