Objectives: The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA-microarray technology might predict disease progression. Methods: Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array (RMA) procedure. Results: Principal component analysis demonstrated that three components explain two thirds of the total variation. Most important parameters for the determination of the colonic gene expression patterns are the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis towards negative values on the axis of the second principal component. The functional annotation analysis suggests that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. Conclusions: Even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, development of stenosis is a parameter that affects the colonic gene expression to some extent.