Rheumatoid arthritis is characterized by massive hyperplasia of synovial tissue. Rheumatoid synovial tissue is characterised by presence of onco-genes and its growth is autonomous, resulting in invasion of synovial tissue in cartilage and bone. Gene transfer to synovial tissue may result in production of toxic products that destroy specifically this tissue.Synoviocytes were isolated from pannustissue of primates (macaca mulatta). In vitro synoviocytes were, in a dose-dependent fashion, easily infected by the adenovirus construct. In vivo, genetransfer to synovial tissue by adenovirus (Ad) was studied in 5 primates suffering from collagen-induced arthritis, an animal model of RA with identical histological features. Inflamed joints of three monkeys were injected with adenoviruses carrying a reportergene, in this case a mixture of Ad-lacZ/Ad-luciferase.In the days after injection, no clinical side-effects occurred. Post mortem examination, three days after injection, did not reveal any abnormalities. Histological examination of virus injected joints, after colouring with X-gal, showed 5 to 10 percent lacZ containing cells in the synovial lining. Location and morphologic appearance of the cells were typical for synoviocytes. Cartilage and articular bone were not stained. No significant difference in inflammation between non-injected and Ad-injected joints was observed. Samples of all organs were analyzed by luminometric methods. Except for one sample that had slightly higher than background counts, none of the samples including liver showed an increase in luciferase counts as compared to controls. Subsequently, a 15 day toxicity experiment in which a mixture of Ad-thymidinekinase and Ad-luciferase was used, revealed no side effects of the adenovirus or presence of virus outside the joints.Conclusion: It is possible to transfect genetic information using an adenoviralvector into synoviumcells in a heavily inflamed joint in primates. This method is safe, with an ideal biodistribution.Currently we are testing if infection of a suicide (TK) gene to the synovium (followed by ganciclovir in order to perform a simple non-mutilating synovectomy without systemic side-effects) is a toxic procedure in monkeys.