The trace element, selenium, is essential for maintaining a viable and responsive immune system. Administered as a chemopreventive agent, it has been shown to significantly reduce cancer mortality and be protective against a number of viral pathogens in a variety of clinical settings. Recent reports indicate that selenium is predictive of HIV-1 related prognosis, and may have an important role in preventing HIV-1 replication. Our studies in HIV-1 seropositive drug users demonstrate that selenium is a powerful predictor of HIV-1 disease progression and mortality. These compelling findings suggest that selenium administered as a chemopreventive agent may effectively modulate HIV disease progression. Our previous experience and a review of the literature indicate that selenium in nutritional doses is feasible and safe in HIV-1 infected individuals. The proposed study is a randomized, double-blind, controlled clinical trial comparing the effects of selenium or placebo in HIV-1 infected male and female drug users. A total of 328 HIV-1 infected adults will be randomized into the trial. At six month intervals, laboratory and clinical markers of disease progression will be evaluated, as well as selenium status, and specific drug use. Compliance to the intervention and potential toxicity will be monitored throughout the trial. This proposed investigation will permit us to determine whether supplemental selenium, as a chemopreventive agent, can enhance the immune system and reduce viral load to slow HIV-1 disease progression in male and female drug users.