Modulation of T cell activity by cyclosporine (CsA) predictably predisposes the host to infection with intracellular pathogens normally controlled by cell-mediated immune mechanisms. Little attention, however, has been paid to the effect of this agent on other cellular defense components associated with pathogens such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. In the present experiments CsA administration exacerbated acute experimentally induced renal infection and led to a 100-fold increase in bacterial numbers. Furthermore, at a time when lesions in the control group were resolving, CsA-treated animals exhibited purulent abscesses involving up to 80% of the surface area of the kidney. Circulating leukocyte numbers were not reduced in CsA-treated hosts and the mechanism for provocation of infection remains to be explained.