Specific polyclonal antisera to human interferon-alpha 1 (HuIFN-alpha 1), human interferon-alpha 2 (HuIFN-alpha 2) and human lymphoblastoid interferon (HuIFN-alpha Ly Namalwa) have been raised in rabbits and sheep. The antisera raised against HuIFN-alpha 1 and HuIFN-alpha 2 strongly neutralized the antiviral activity of their homologous IFN-alpha subtypes, but were less active against the heterologous IFN-alpha subtypes and preparations containing mixtures of IFN-alpha subtypes, e.g. human leukocyte interferon (HuIFN-alpha Le). Antisera raised against HuIFN-alpha Ly Namalwa strongly neutralized the antiviral activity of all IFN-alpha-containing preparations and showed weak cross-reactivity with human interferon-beta (HuIFN-beta). Neither anti-HuIFN-alpha 1 nor anti-HuIFN-alpha 2 could be demonstrated to neutralize the antiviral activity of HuIFN-beta. A number of monoclonal antibodies to HuIFN-alpha 2 have been prepared and these were found to neutralize HuIFN-alpha 2 antiviral activity to varying degrees, but not to neutralize the heterologous subtype HuIFN-alpha 1, preparations containing mixtures of IFN-alpha subtypes or HuIFN-beta.