Primary and passaged human synovial cell cultures inoculated with wild-type and vaccine strains of rubella virus were incubated at 32 C and 37 C. At 32 C, the temperature close to that in human peripheral joints, infection persisted with extracellular virus titers of approximately 10(4) fluorescent focus-forming units/ml. Extracellular titers at 37 C first stabilized at one-tenth the level of the titers at 32 C and then declined after 20 days to undetectable levels. Cellular expression of viral antigen rose at 32 C and fell at 37 C. Infection was noncytocidal at all stages. Virus yields reflected the temperature in the subsequent incubation rather than during virus adsorption. Interferon was found only in cultures held at 37 C and was mainly alpha with a minor beta fraction, a result suggesting retention of functional characteristics of the type A macrophage-like synovial cell. We conclude that persistent infection of synovial tissue in vivo is a feasible explanation for the presence of rubella virus in peripheral joints of patients with chronic arthritis.