There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjøgren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint.