ABSTRACT: Inoculation of endophyte-free (E-) Theobroma cacao leaves with Colletotrichum tropicale (E+), the dominant foliar fungal endophyte in healthy T. cacao, induced significant changes in the expression of hundreds of host genes. Further, E+ leaves exhibit enhanced pathogen resistance, increased lignin and cellulose content, reduced maximum rates of photosynthesis (Amax), and enrichment of nitrogen-15 and carbon-13 isotopes that all correspond to the changes in expression of specific functional genes in related pathways. Moreover, a cacao gene highly up-regulated in E+ leaves increases pathogen resistance apart from any direct endophyte effects. Thus, benefits of increased pathogen resistance in E+ plants are partially due to enhanced induction of intrinsic host defense pathways, and potential costs include reduced photosynthetic capacity and endophyte metabolism of host tissues. Similar effects are likely to be properties of most plant-endophyte interactions, suggesting general relevance to the design and interpretation of studies of genetic and phenotypic expression in plants. This was a time course experiment, which objective was to assess gene expression changes in leaves of Theobroma cacao due to inoculation with endophyte Colletotrichum tropicale, over a period of two weeks. Three un-inoculated T. cacao leaves (E-) were collected at time 0, just prior to inoculation, and four T. cacao leaves inoculated with C. tropicale (E+) were collected at 3, 7, and 14 dpi, each leaf from a different plant. Sampled leaves were of developmental stage C-D (MejM-CM--a et al. 2012). MejM-CM--a, L.C., Guiltinan, M., J. , Shi, Z., Landherr, L., and Maximova, S., N. (2012). Expression of Designed Antimicrobial Peptides in Theobroma cacao L. Trees Reduces Leaf Necrosis Caused by Phytophthora spp, in Small Wonders: Peptides for Disease Control. American Chemical Society), 379-395.