The antiviral activity of alpha-interferon (IFN-alpha) produced by human leukocytes in response to viral infection has been considered to be independent of the virus which induced its production. Recently, however, IFN-alpha has been found to include at least eight different subtypes, as indicated by measurement of antigenic variability, DNA hybridization and amino acid sequencing. We considered the possibility that interferon heterogeneity may play a part in enhancing host antiviral defence and now present data suggesting that purified human macrophages, when exposed to different viruses, produce interferons having differing spectra of antiviral activity. These findings may provide a functional correlation for IFN-alpha heterogeneity.