In the experimental Candida albicans intravenous challenge model, the kidney is one of the main organs involved in disease. In progressive infection, fungal burdens are found to increase over time, with rapid increases occurring from 24 h postinfection. Renal transcriptional responses were analyzed at this time in the kidneys of mice infected by either a virulent or an attenuated C. albicans strain, allowing comparison of host responses in progressive and nonprogressive infection. The results of this study demonstrate that both infections share a common transcriptional response, consisting of functions associated with the acute-phase reaction. In addition, challenge with the virulent strain led to a massively increased expression of cytokine genes, other innate response genes and genes suggestive of initiation of the adaptive immune response. This immune response to C. albicans infection, which occurs only in progressive infection, may contribute to development of sepsis and, ultimately, host death.