Previous reports by others of resistance of cultured rheumatoid synovial cells to experimental virus infection prompted extension of such studies to rheumatoid fibroblasts from other tissues. Strains of cells derived from rheumatoid skin, synovium and a nodule and from nonrheumatoid skin and synovium were inoculated in vitro with rubella virus (RV). All of the tissues studied proved equally susceptible to RV infection.Rheumatoid synovial cells grown as a monolayer in tissue culture differ from cells derived similarly from patients with other types of arthritis. To summarize briefly, rheumatoid cells show increased lysosomal activity (1 ), solubilize cartilage matrix (2), have a decreased life span (3), form hyaluronic acid at an accelerated rate but of abnormal intrinsic viscosity (4, 5), metabolize glucose more rapidly (5), are less responsive to hydrocortisone suppression in formation of hyaluronate (4), are less affected by polypeptide "activator" (5), and are reported to be completely resistant to infection with RV (6) and relatively resistant to infection with Newcastle Disease Virus (NDV) (7). The increased lysosomal activity, the more rapid metabolism of glucose and the (1,3, 5). These observations demonstrate that cells grown in vitro from rheumatoid synovium retain properties of the intact synovium from which they were derived. The studies (6, 7) reporting resistance of cultured rheumatoid synovial fibroblasts to experimental virus infection, therefore have increased speculation that a virus infection is important in the pathogenesis of rheumatoid arthritis (RA) (3, 5, 6,12).The present study was undertaken to determine if fibroblasts derived from rheumatoid skin and rheumatoid nodules would also show the resistance to RV infection reported by Grayzel and Beck (6) for rheumatoid synovial fibroblasts. For this purpose, rheumatoid skin and nodule fibroblasts were inoculated with RV. Strains of nonrheumatoid skin, rheumatoid synovium and nonrheumatoid synovium served as controls for comparison. Rubella virus was assayed from the supernatant medium of virusinfected cultures.Resultant data indicated that fibroblasts from rheumatoid skin and a single rheumatoid nodule uniformly were susceptible to RV infection. Unexpectedly, rheumatoid synovial fibroblasts also showed no resistance to RV infection under the conditions employed.