The use of mRNA to transfer genetic information into mammalian somatic cells in vivo or ex vivo may be advantageous in a number of gene therapy protocols. Success in utilizing in vivo RNA delivery for transgene expression has been extremely limited, partially due to RNA instability and to the lack of an efficient intracellular delivery mechanism applicable to a wide variety of tissue or organ systems. We report here that a particle-mediated gene delivery technology can be used to effectively deliver RNA molecules into a number of mammalian somatic tissue types. Expression from RNA transcripts of three reporter genes, firefly luciferase, human growth hormone and human alpha-1 antitrypsin, was detected in monolayer and suspension cell cultures bombarded in vitro, and in in vivo bombarded rat liver tissues, and mouse liver and epidermal tissues. Gene gun treatment of mouse epidermis in vivo with human alpha-1 antitrypsin messenger RNA elicited a strong, consistent antibody response which showed an increased titer with subsequent boosts. Results from this study point to future opportunities of applying RNA delivery techniques for transgenic studies, genetic vaccination, and gene therapy.