We propose a two-year study of acute hepatitis C virus (HCV) infection in young injection drug users (IDUs): early identification of seroconversion so as to examine the immunologic responses to acute infection and to facilitate tests of early treatment intervention candidacy in young IDU. This study will be conducted in a previously recruited cohort of HCV-negative young IDUs in San Francisco, who have already demonstrated an extremely high HCV seroconversion rate (28% ppy). This collaboration will involve epidemiologists, clinicians and immunologists. We will identify acute HCV infection using minimally invasive diagnostic methods. We have preliminary studied identifying early HCV infection by the presence of HCV viral RNA (HCV-RNA) using nucleic acid amplification technology (NAT) and the absence of anti-HCV by EIA in a single blood sample. We will measure the subsequent rate of clearance of infection ("resolution"), and study the immunology of viral clearance in young IDU. Lastly, because of recent evidence suggesting that treatment of acute HCV may prevent chronic infection, we will investigate the clinical features of acute HCV to be monitored prior to and during an interferon-based early treatment regimen, as well as explore early HCV treatment readiness in newly-infected young IDUs. The specific aims are: 1. We will identify early HCV infection using an RNA-amplification technology in seronegative young IDU, IDU and estimate rate of viral clearance. 2. We will examine how the spectrum of cytotoxic T lymphocyte (CTL) responses and antibody responses influence the outcome of HCV infection with a view to developing targets for vaccine-inducible responses. 3. We will examine whether evolution within CTL targets ("epitopes") influences resolution or persistence of HCV infection. 4. We will examine the clinical and laboratory features of acute HCV that may determine early HCV treatment candidacy and explore the readiness of newly infected young IDU for an early treatment intervention. 5. We propose to continue to follow current HCV seronegative participants of the UFO cohort for two years. Participants who are seronegative and viremic (HCV RNA positive) or become EIA-2 positive will be enrolled in the acute infection study. We anticipate that 64 participants will become infected with HCV over the two-year period, and that 46 (72%) will be effectively followed and observed. This cohort has an active participant group, a high seroconversion rate, and provides significant opportunity for study of acute HCV infection.