Plant pathogenic Phytophthora species are predicted to encode a large arsenal of 'effector' proteins that target and disrupt normal host cell function, but genes regulated by effectors are difficult to distinguish from those more generally regulated by microbe associated molecular patterns (MAMPs). To help make this distinction, expression studies of host-Phytophthora interactions can be compared to reveal patterns of gene regulation indicative of effector activity. The recently sequenced tropical fruit tree, Carica papaya, contains fewer genes than Arabidopsis and is highly susceptible to the broad-host-range pathogen P. palmivora, offering a new system for comparative genomics. In this study, genes isolated from the transcriptome of C. papaya seedling roots inoculated with P. palmivora, were evaluated for pathogen-regulation. Of these genes, a predicted peroxidase, ß-1,3-glucanase, ferulate 5-hydroxylase, and hypersensitive-induced response protein were pathogen upregulated, while a second peroxidase (Cp9) and aquaporin (Cp15), both with normally high root expression, were downregulated. Genes from other plants with similar expression responses to Phytophthora were identified from previously reported studies and evaluated for protein sequence similarity. Interestingly, as for papaya, Phytophthora also downregulates homologs of Cp9 and Cp15 in Glycine max and Solanum tuberosum, respectively. Because peroxidases associated with defense are generally upregulated during infection and the regulation of aquaporins have been cited in cases of both plant (Opperman et al. Science 263:221-223, 1994) and animal disease (Guttman et al. Cell Microbiol 9:131-141, 2007), Cp9 and Cp15 are potential cross-species effector targets. With whole-genome C. papaya microarrays forthcoming, this study highlights papaya as a resource for comparative genomic studies of Phytophthora-plant interaction.