The objective of this study was to determine effects of Arg supply on the expression of a se-lect set of genes related to AA metabolism, vascular function, cellular regulation of protein synthesis, and cell differentiation and turnover between the mammary and longissimus dorsi tissues. Six rumen-cannulated, lactating Holstein cows were used in a replicated 3 × 3 Latin square design with 14-d periods. Treatments were continuous abomasal infusion that supplied 0 (ARGx0), 49.2 (ARGx1), and 98.4 (ARGx2) g/d Arg in an otherwise complete AA mixture at 1054 g/d. Arg appeared to support milk production and maintain the protein synthesis set-point in the mammary glands through up-regulation of genes related to Pro synthesis, AA transport, and protein synthesis regulators, whereas gene expression in muscle was consistent with an optimized response to Arg supply and supported the milk production setpoint by act-ing as a buffer to supply additional AA to the mammary glands.