Gene expression profiling may provide leads for investigations of the molecular basis of functional declines associated with aging. In this study, high-density oligonucleotide arrays were used to probe the patterns of gene expression in skeletal muscle of seven young women (20-29 years old) and eight healthy older women (65-71 years old). The older subjects had reduced muscle mass, strength, and peak oxygen consumption relative to young women. There were approximately 1000 probe sets that suggested differential gene expression in younger and older muscle according to statistical criteria. The most highly overexpressed genes (>3-fold) in older muscle were p21 (cyclin-dependent kinase inhibitor 1A), which might reflect increased DNA damage, perinatal myosin heavy chain, which might reflect increased muscle fiber regeneration, and tomoregulin, which does not have a defined function in muscle. More than 40 genes encoding proteins that bind to pre-mRNAs or mRNAs were expressed at higher levels in older muscle. More than 100 genes involved in energy metabolism were expressed at lower levels in older muscle. In general, these results support previous observations on the differences in gene expression profiles between younger and older men.