A monoclonal antibody to human interferon-alpha (IFN-alpha) was produced using affinity-purified IFN-alpha, that reacted with recombinant human IFN-alpha 2, but not with IFN-alpha 1, IFN-alpha M1 or IFN-beta. Indirect immunofluorescence using this monoclonal (designated 6C3) and anti-IFN-alpha polyclonal antibodies identified cells expressing IFN-alpha. After Sendai virus induction of normal human buffy-coat cells the proportion of monocytes and lymphocytes expressing IFN-alpha rose progressively from 0% to 50% and 34% respectively, preceding peak IFN-alpha titres in the culture supernatants. Around 80-90% of polymorphs were IFN-alpha-positive using both antisera, with or without IFN induction, although very little IFN bioactivity was released to the supernatant of polymorph cultures after IFN induction. Sections of hepatitis B virus infected human liver tissue showed foci of IFN-alpha-positive infiltrating mononuclear cells and (to a lesser extent) fibroblasts in patients who had active cirrhosis and evidence of virus replication. These findings suggest that polymorphs constitutively express IFN-alpha 2 related antigenic activity, whose biological activity is at present unknown; and demonstrates the identification of IFN-alpha-expressing cells in sections of tissue undergoing natural virus infection.