We have investigated the feasibility of using high-titer murine leukemia virus-based retroviral vectors to deliver exogenous genes to naive and chronically inflamed knee joints of rabbits in vivo. Intraarticular injection of retrovirus encoding beta-galactosidase (beta-gal or lacZ) was found to transduce synoviocytes in both naive and inflamed joints, but a significantly higher number of lacZ+ cells were found in inflamed knees. Using a retrovirus encoding a secretable marker, human growth hormone (hGH), quantitative comparison of ex vivo and in vivo gene delivery methods demonstrated that transgene expression following in vivo gene transfer was at least equivalent to that of the ex vivo method in inflamed knees. In addition, hGH transgene expression was maintained for at least 4 weeks. These experiments suggest that high-titer retroviral vector could be used for efficient in vivo gene transfer to inflamed joints in patients with rheumatoid arthritis (RA).