Ribozymes are a new pharmaceutical class of reagents that offer potential in treating a number of different medical disorders, including infectious diseases and cancer. As a first step towards using ribozymes for the treatment of liver disorders such as viral hepatitis, adenovirus vectors that contain a ribozyme expression cassette under the control of different promoters directed against human growth hormone (hGH) were constructed and infused into transgenic mice that produce hGH from the gastrointestinal tract and liver. Adenovirus-mediated transfer of expressed ribozymes resulted in up to a 96% reduction of hepatic hGH mRNA over a period of several weeks in the transgenic mouse model. Furthermore, the concentration of ribozyme RNA correlated with the degree of hGH mRNA reduction. This study clearly demonstrates that ribozymes can function during the period of expression in an intact organ after somatic gene transfer.