This study compared the effects of growth hormone (GH) and β-adrenergic agonist (BA) on porcine muscle transcriptome and blood metabolome. Duroc × (Landrace × Large White) gilts (77 ± 7.1 kg, n = 165) were all fed a high protein/energy diet ad libitum, with the GH group receiving an intramuscular injection, 10mg once every 2d of porcine GH (Reporcin, Zamira), the BA group receiving Ractopamine at 20mg/kg feed, whereas the control group just had feed. Pigs were treated for 1, 3, 7, 13d (n = 10 per treatment for each period) and 27d (n = 15 per treatment for each period). After each treatment period muscles were harvested and blood collected, then plasma immediately prepared. The remaining carcass was incinerated. Plasma was analyzed by Metabolon’s biochemical platform technology. Total RNA from LD was extracted and subjected to transcriptome analysis (Agilent pig microarray) followed by gene cluster analysis using MaSigPro. Gene expression was verified by quantitative RT-PCR. Protein expression was determined by Western blot. Treatment groups were compared by 2-way ANOVA (Genstat). The BA treatment increased Vastus Lateralis weight (P < 0.001), and induced a switch to faster muscle fiber type in Longissimus dorsi (LD), as myosin heavy chain isoform IIB gene expression was increased (P < 0.001). Within 1d of treatment plasma fatty acids were increased in BA, but not GH (P < 0.05). Both GH and BA decreased certain plasma amino acids, such as lysine (P < 0.05), but only GH decreased the concentration of others, such as serine (P < 0.05) and glycine (P < 0.05). Only GH increased glucose (P < 0.05) but there was no effect of either GH or BA on lactate (P > 0.1). Predominant effect of treatment was a BA coordinate increase in LD serine synthesis pathway gene expression (PHGDH, P < 0.001; PSAT, P < 0.001; PSPH, P < 0.001) by 3d, which was confirmed at the protein level, as PHGDH was increased with BA at 7d (P < 0.001). The effect of GH and BA treatment on metabolism appears to lead to differential effects on muscle mass, with BA potentially elevating serine synthesis, which could lead to the generation of metabolites required for growth.