Chronic hepatitis C is the most common infectious disease among injection drug users (IDUs). Because of the allegedly poor compliance of IDUs with treatment requirements and conditions, hepatologists recommend treatment only if former IDUs have spent 6 to 12 months drug free. The aim of this prospective study was to investigate whether opiate-dependent IDUs with chronic hepatitis C virus (HCV) infection can be treated successfully with interferon. Eligibility for the study meant IDUs had to be HCV-RNA positive by polymerase chain reaction. Subsequently 50 inpatients were enrolled during detoxification treatment. HCV treatment was started with interferon alfa-2a (through 1998) or a combined regimen consisting of interferon alfa-2a and ribavirin (begun in 1998). All patients were treated and supervised by specialized physicians in both hepatology and addiction medicine. The end point for this study was defined as a loss of detectable serum HCV RNA at week 24 after treatment. The rate of sustained virologic response was 36%. Sustained response rates were not significantly different for patients who relapsed and returned to treatment (53%), relapsed and did not return to treatment (24%), or did not relapse (40%; P > .05). During the 24 weeks after treatment, we were unable to detect any reinfection, even among patients who injected heroin during this period. This surprising result should be examined in further studies. In conclusion, HCV-infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa-2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine.