The Affymetrix canine GeneChip with 23,836 probe sets was used to look for cartilage genes that are significantly altered in response to mechanical impact. The model using canine articular cartilage explants loaded in vitro has been described previously (Chen et al., J Orthop Res 19:703-711, 2001). It is our hypothesis that genes that are activated or repressed in articular cartilage after impact injury initiate cartilage degeneration, leading to osteoarthritis in dogs. Gene expression of known cartilage genes was generally consistent with cartilage biology. A total of 528 genes were significantly (P < .01) up- or down- regulated in response to mechanical damage. After applying the strict Bonferroni correction, 172 remained significantly affected. One of these genes, MIG-6/gene 33, was chosen for verification by real- time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). A 3.8- fold increase in expression was confirmed, consistent with the microarray chip data. Deficiencies in the current annotation of the canine chip are discussed. Gene expression studies with the Affymetrix canine GeneChip are potentially valuable, but await more complete annotation.