Four adult myosin heavy chain (MHC) genes, each encoding a specific motor protein impacting contractile velocity and hence performance, are expressed across the spectrum of rodent skeletal muscles of mammals, including humans. In the rat, the slow type I MHC gene is located on chromosome 15; whereas, the three fast types, IIa, IIx, and IIb MHC genes, are clustered on chromosome 10 in a tandem alignment (IIa: IIx: IIb) and referred to as the type II MHC gene locus. The goal of this presentation is to give evidence that the plasticity of the MHC genes is regulated at the transcriptional level, which can be examined by several different but interrelated approaches. These include: 1) studies examining the endogenous gene via analyses of either the innate transcription product, e.g., pre-mRNA, and/or transfected promoter- reporter constructs, the latter of which can be manipulated to identify key sequences of regulation; 2) novel studies involving the expression of anitsense RNA on the type II gene locus, which show the ability of down stream MHC gene to inhibit the up-stream gene, which is manifest in models such as muscle unloading and muscle overloading: and 3) epigenetic regulation involving changes in the chromatin/ histone remodeling (acetylation and methylation at key histone sites) , which alter inherent transcription activity of the target MHC genes in response to specific stimuli. In the presentation we will present examples of each of these types of MHC transcriptional regulation using the modals of hind limb suspension, spinal isolation, and resistance loading exercise. Supported by NIH AR 30346.