The role of the immune response in pyelonephritis was investigated by manipulation of the host's immune capacity using the immunosuppressive drugs 6-mercaptopurine, cyclophosphamide and thiamphenicol. Treatment with 6-mercaptopurine depressed the humoral immune response but did not have an adverse effect on the course of renal infection. Thiamphenicol administration prevented the development of pathological lesions but this was due to the anti-bacterial activity of thiamphenicol and not to its immunosuppressive activity. Pyelonephritic animals treated with cyclophosphamide did not produce anti-bacterial antibody. Despite this, cyclophosphamide-treated animals were able to eliminate organisms more readily from the infected kidney than untreated animals with a normal humoral immune response. We believe that blocking of the phenomenon of immunological enhancement explains these unexpected results and that the immune response to renal infection may have an immunoenhancing role protecting the bacterial cell from otherwise effective host defence mechanisms.