Mumps virus (MuV) is known to be associated with acute arthritis and may also have a role in chronic inflammatory joint disease. The mechanism of induction of joint inflammation is not known but may be associated with direct invasion of joint tissue. To investigate the possibility of persistent intra-articular infection, the interaction of MuV with primary cells from normal human joint tissue was examined. These mixed cultures of synovial membrane cells and chondrocytes were found to be semi-permissive to the virus; only a small proportion of cells (5 to 20%) were infected and produced low titres of progeny virions. In addition, little viral antigen was detected on the cell surface relative to that found on Vero cells. This restricted infection of synovial membrane cells was related to a severely decreased synthesis of the viral glycoproteins, fusion and haemagglutinin-neuraminidase, and the membrane protein in comparison to the levels found in Vero cells. Persistent infections were readily established and could be maintained for 2 to 3 months. During the first month, the infection remained highly focal and supernatant viral titres were low. Thereafter both the percentage of infected cells and viral titres increased until finally the cultures were killed. No evidence was obtained for the generation of temperature-sensitive mutants or defective interfering particles during long-term infection, but the persistent virus derived from the cultures gave cloudy plaques and induced no fusion in Vero cells until passaged. This study has shown that human synovial tissue cells have the intrinsic ability to support MuV replication and persistence which may be important in the pathogenesis of mumps arthritis.