It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic disease. Particles resembling retroviruses have been reported in tissue from patients with Sjogren\'s syndrome, lupus and rheumatoid arthritis, and molecular mimicry between retroviral antigens and host proteins has been proposed as a mechanism of induction of autoimmunity. Since 1980, four distinct human infectious retroviruses have been discovered, HTLV-I, HTLV-II, HIV-1 and HIV-2. We recently cloned part of a new human retrovirus genome, designated human retrovirus-5 (HRV-5) and demonstrated that this is not endogenous and is therefore a novel infectious retrovirus. Because symptoms resembling arthritis, polymyositis and Sjogren\'s syndrome occur in individuals infected with HTLV-I and HIV-1, we investigated the possibility that HRV-5 was associated with idiopathic rheumatic disease. Using nested PCR, HRV-5 we demonstrated that proviral DNA was present in approximately 50% of synovial samples of arthritic joints and was also found in over 10% of blood samples of patients with rheumatoid arthritis and systemic lupus erythematosus. HRV-5 proviral DNA was not detectable in affected tissues of autoimmune diseases and was found in only one of over 200 tissues taken at autopsy from non-rheumatoid patients. Sequence analysis of the amplified viral segment showed genetic variation between samples with maintenance of the open reading frame typical of a replicating infectious retrovirus. Thus HRV-5 appears to be a human retrovirus found with a very low genome copy number in most tissues, but which is increased to detectable levels in inflamed joints and blood from patients with rheumatic disease. Whether HRV-5 is aetiologically important in these diseases remains to be determined.