The effects of dietary protein and age on the skeletal muscle transcript profile were assessed in 12 younger (21–43 y) and 10 older (63–79 y) men who completed three controlled feeding trials with protein intakes of 63% (P63), 94% (P94), and 125% (P125) of the recommended dietary allowance (RDA). On d 12 of each trial, a fasting state sample of the vastus lateralis was obtained and Affymetrix U133A Plus 2.0 genechips were used to assess global changes in mRNA levels. 958 transcripts (TR) were differentially expressed (P<0.05) with diet and 853 with diet‐by‐age (P<0.05) using ANOVA. Independent of age, at P63 TR associated with ubiquitin‐dependent protein catabolism and muscle contraction were up‐regulated (UP). At P63 and P94 TR related to apoptosis were UP and TR related to cell differentiation; muscle and organ development; extracellular space; and responses to stimuli and stress were down‐regulated. The diet‐by‐age effect on protein modification (folding) TR was consistent with the older males being less responsive to anabolic stimuli (lower protein synthesis at P125) and more responsive to a catabolic state (protein breakdown at P63). In summary, changes in skeletal muscle mRNA levels to protein intakes near or below the RDA are indicative of an early accommodative response in both age groups, and especially older males.Support: USDA 03‐35200‐13779 & 98‐35200‐6151; NIH R01 AG15750, and Purdue Research Foundation.