Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae. The splenic marginal zone is essential in the initiation of immune responses to S. pneumoniae. We analyzed effects of multidose combination chemotherapy on B-cell subpopulations. Immune response capacity was evaluated by using Pneumovax (PPS) or Tetavax (TT) as antigenic challenge. Three days after finishing therapy, all B-cell subpopulations in bone marrow and spleen were severely reduced, including the mature marginal zone B-cell population. When analyzing the anti-PPS immune response capacity at 3 days after finishing therapy, we found that the IgM antibody levels did not differ significantly from control immunized rats. The IgG antibody levels were significantly lower compared to control immunized rats but still significantly higher compared to unimmunized rats. The depletion of marginal zone B cells by multidose combination chemotherapy most likely contributes to the prolonged period that patients are at risk for developing severe infections after chemotherapy, despite the capacity to generate sufficient antibody levels. It is conceivable that the local (temporary) loss of immunological memory, together with the supposed inability to generate a Immoral response in a short time frame, plays an important role in this vulnerability. (C) 2003 Elsevier Science (USA). All rights reserved.