In 1994, an outbreak of hepatitis C virus (HCV) infection, genotype 1a, occurred in 30 hypogammaglobulinaemic patients in the UK from one batch of contaminated anti‐HCV screened intravenous immunoglobulin. This study aimed to study prospectively the outcome of HCV in hypogammaglobulinaemic patients, and to assess the response to early treatment with interferon‐alpha, 6 million units three times weekly for 6 months. Data were collected using standardized questionnaires. Five patients with secondary hypogammaglobulinaemia due to lymphoid malignancy were not treated and all have died of their primary malignancy. Of 25 patients with primary hypogammaglobulinaemia, one resolved HCV infection before treatment, 17 commenced on treatment, and seven declined or treatment was contra‐indicated. Thirteen of 17 patients completed therapy and seven (54%) have a sustained response (normal transaminases, negative serum HCV RNA) at 6 and 12 months after treatment. Two of the 12 patients with primary hypogammaglobulinaemia, who were not treated or failed to complete treatment, have cleared the virus. Liver biopsy was performed in patients not clearing HCV and was abnormal in all. Four patients developed liver failure within 2 years, of whom three have died and one has been successfully transplanted. In conclusion, HCV can cause rapid severe liver disease in hypogammaglobulinaemic patients. Early treatment with high‐dose interferon‐alpha results in a high clearance of HCV.