Background & Aims: Following massive small bowel resection (SBR), the remnant intestine undergoes an adaptive process characterized by increases in a number of physiologic and morphologic parameters. These changes are the result of a stimulus that increases crypt cell mitosis and augments cellular progression along the villus axis. To better define this process, we identified patterns of gene expression specifically within adapting intestinal crypt cells following SBR. Methods: Laser capture microdissection was used to isolate mouse intestinal crypt cells following SBR or sham operation. Multiple biological and technical complementary DNA microarray replicates allowed rigorous statistical analyses for identification of important expression profiles. Major groups of genes were classified as to site of action, functional pathway, and possible regulatory groups. Results: A total of 300 genes differentially expressed at significant levels within adapting crypt enterocytes were analyzed. Comparison of this list of differentially expressed adapting crypt cell genes with a generalized mouse gene expression database (from 82 developing and adult mouse tissues) showed the greatest overlap with developing and immature intestinal tissues. We identified prominent groups of genes involved with cell growth, signal transduction, and nucleic acid binding. Genes not previously shown to be involved with adaptation or development and maturation were identified. Conclusions: Identification of similar genes coordinately regulated during both adaptation and development, processes that share key morphologic features, provides a basis for new mechanistic insights into these shared characteristics.