Deficiency of 2-laminin (merosin) underlies classical congenital muscular dystrophy in humans and dy/dy muscular dystrophy in mice, and causes severe muscle dysfunction in both species. To gain greater insight into the biochemical and molecular events which link 2-laminin deficiency with muscle fiber necrosis, and the associated compensatory responses, gene expression profiles were characterized in diaphragm muscle from 8-week old dy/dy mice using oligonucleotide microarrays. Compared with age-matched normal muscle, dystrophic diaphragm was characterized by predominantly augmented gene expression, irrespective of the fold-change threshold. Among the 69 genes with at least ±2-fold significantly altered expression, 30 belonged to statistically over-represented gene ontology (GO) biological process groups. These covered four specific themes: development including muscle development, cell motility with an emphasis on muscle contraction, defense/immune response, and cell adhesion. An additional 11 gene transcripts were assigned to more general over-represented GO biological process groups (eg. cellular process, organismal physiological process); the remaining 28 did not belong to any over-represented groups. GO cellular constituent assignment resulted in the highest degree of over-representation in extracellular and muscle fiber locations, whereas GO molecular function assignment was most notable for various types of binding. RT-PCR was performed on 38 of 41 genes with at least ±2-fold significantly altered expression that were assigned to over-represented GO biological process groups, with expression changes verified for 36 of 38 genes. These results indicate that several specific groups of genes have altered expression in response to genetic 2-laminin deficiency, with both similarities and differences compared with data reported for dystrophin-deficient muscular dystrophies.