In order to characterize expression of Homers in mouse brain and peripheral tissues we have developed a coupled reverse transcription (RT)-PCR/restriction digestion approach. This has allowed us to determine the molecular composition and relative levels of the constitutive expression of the Homer-1, -2 and -3 mRNAs across mouse tissues. We report here that mammalian brain constitutively expresses high levels of the Homer-1, -2 and -3 mRNAs. Expression of the Homer-1 mRNAs reaches 66% of the brain total Homer mRNAs expression, followed by Homer-3 mRNA (22%) and Homer-2 mRNAs (12%). Quantitative RT-PCR analysis and the Western blotting using pan-Homer antibody revealed that mouse heart, skeletal muscle and diaphragm constitutively express high levels of the Homer proteins and their mRNAs. We have shown that the molecular profile of expression of Homer-1, -2 and -3 mRNAs in muscle containing tissues resembles that obtained for mammalian brain.