The objective of this dissertation was to investigate the manipulation and regulation of post-weaning growth in the pig. Specific objectives, as reflected in the individual chapters of this thesis, were to investigate the basis for differences in post-weaning growth rate and the modification of growth achieved through the use of two feed additives: tylosin phosphate (TP) and ractopamine hydrochloride (RAC). In the first experiment, 18 cannulated barrows (initial BW = 32.6 ± 1.2 kg) were utilized to evaluate the impact of TP on energy and nutrient digestibility in growing pigs fed corn-soybean meal or corn-soybean meal-distillers dried grains with solubles (DDGS) based diets. Results of this study indicated that the ileal digestibility of all indispensible AA, except leucine, and the apparent total tract digestibility of energy and fiber was lower (P < 0.05) in corn-soybean meal-DDGS-based diets than in corn-soybean meal-based diets. Tylosin phosphate did not affect digestibility of AA or digestibility and gastrointestinal tract flow of energy (P > 0.10). A second experiment was conducted to determine if a higher fiber diet alters the response of finishing pigs to TP and RAC in terms of N and water utilization and energy digestibility using 72 gilts (initial BW = 107.4 ± 4.2 kg) housed in individual metabolism pens. Ractopamine HCl improved ADG (P < 0.0001), feed efficiency (P < 0.0001), and N retention (P < 0.001) and tended to increase daily water intake (P < 0.10), and the response to RAC was similar in both corn-soybean meal based and corn-soybean meal-DDGS based diets. Tylosin phosphate tended to increase ADG in pigs fed corn-soybean meal based diets (P < 0.10), but not in diets containing 30% DDGS (P > 0.10), but this response was not accompanied by changes in N balance or energy digestibility. A third experiment was conducted to develop a better understanding of the metabolic basis for poor post-weaning growth in pigs using RNA-Seq transcriptional profiling of skeletal muscle and adipose tissue. A total of 1,054 pigs were reared in commercial conditions and weighed at birth, weaning, and 3 weeks post-weaning. Transition average daily gain (tADG) was calculated as the average daily gain for the 3-wk period post-weaning. Nine pigs from each of the lowest 10th percentile (low tADG) and the 60th-70th percentile (high tADG) for transition ADG were harvested at 3 weeks post-weaning. Differential expression analysis was conducted in longissimus dorsi muscle (LM) and subcutaneous adipose tissue. In LM, 768 transcripts were differentially expressed (DE), and no DE transcripts were identified in adipose tissue. The group of DE genes with lower expression in LM of low tADG pigs was enriched in genes with functions related to muscle contraction, glucose metabolism, cytoskeleton organization, muscle development, and response to hormone stimulus (enrichment score > 1.3). The list of DE genes with higher expression in low tADG LM was enriched in genes with functions related to protein catabolism (enrichment score > 1.3). Analysis of known gene-gene interactions identified forkhead box O1 (FOXO1), growth hormone (GH1), and the glucocorticoid receptor (NR3C1) as possible regulators of these differences in gene expression. Differences in transcript abundance between poor transitioning pigs and their contemporaries indicate a possible shift to decreased protein synthesis, increased protein degradation, and reduced glucose metabolism in the LM of low tADG pigs. Post-weaning growth is a complex biological process that is influenced by nutritional, genetic, and environmental factors. These experiments provide findings that enhance the understanding of the manipulation and regulation of post-weaning growth in the pig.