Candida albicans, a commensal of the gastrointestinal and uro vaginal tract can cause life-threatening infections under conditions of lowered immunity of the host. The changes in the host environment that are sensed by the pathogen which elicit this response have not yet been clearly identified. We report here that co-incubation with a macrophage cell line in vitro for extended period of time (16 h) leads to lysis of the macrophage cells. The altered condition in growth medium induces differential gene expression of sets of genes. Specifically genes involved in galactose, protein, and lipid metabolism and stress response undergo concerted changes in their transcript levels. Promoter analysis of differentially expressed genes revealed presence of CPHI and EFGI transcription factor binding sites. Based on the gene expression profiles and mutant studies we propose that this morphogenetic response of C. albicans under the conditions used in these experiments is mainly through the pathways controlled by the above two regulators and not through the RIM101-dependent pathway. (c) 2005 Elsevier Inc. All rights reserved.