To investigate the host-cell response to infection with the obligate intracellular pathogen Toxoplasma gondii, the transcriptional profiles of infected and uninfected human fibroblasts (HFF) were determined by hybridization to gene arrays representing nearly 600 genes. Transcripts that displayed a greater than five-fold increase in level relative to uninfected controls were also examined by RT-PCR and Northern analysis, resulting in the identification of 13 genes that were strongly up-regulated after infection with T. gondii. Comparisons with the transcriptional profiles of fibroblasts infected with Salmonella typhimurium and Chlamydia trachomatis allowed the identification of genes which are specifically induced in T. gondii-infected cells. While most of the up-regulated genes were induced on infection with all three pathogens, the genes for the transferrin receptor and MacMARCKS were up-regulated in Toxoplasma-infected fibroblasts only. Expression of the transferrin receptor protein was examined by Western analysis and found to be specifically elevated in Toxoplasma-infected fibroblasts. Genes which are specifically induced in T. gondii-infected cells are particularly interesting for further studies, since they might be used to dissect specific interactions of this pathogenic parasite with its host cell.