Tremendous progress has been made in the identification of the stimulatory molecules that regulate growth, the mechanisms of action, and the potential application of these molecules for livestock production. A parallel and significant effort is now focused on the discovery and development of economically feasible gene delivery technologies. Plasmid-mediated GHRH gene transfer has emerged as an excellent candidate for agricultural applications to optimize production and animal welfare. We have engineered a GHRH-expressing plasmid that is efficiently expressed in skeletal muscle following intramuscular injection enhanced by electroporation. The GHRH is synthesized in the injected muscle, from which it is secreted to circulate and stimulate normal pituitary GH production and release. Young pigs directly injected with as little as 0.1 mg of a GHRH-expressing plasmid had greater (P < 0.01) weight gain than controls, and a increase (P < 0.05) in fat-free mass. We also have demonstrated that the offspring of gilts injected intramuscularly at d 85 of gestation with a GHRH-expressing plasmid have optimized growth characteristics due to both improved intrauterine weight gain and enhanced maternal lactation performance. Thus, the piglets from treated gilts were larger at birth and weaning compared to controls and reached market weight earlier (P < 0.001). Additionally, pituitaries collected from this group contained an increased number of somatotrophs and lactotrophs (P < 0.001) at birth and at 100 kg. An additional advantage of administering the GHRH plasmid to the gilt compared with the administration of growth-promoting agents to the individual adult animal is a substantial decrease in offspring morbidity and mortality (P < 0.01), which has always represented a major economic loss for the swine industry.