Here we report on the antiviral effects of two commercially available natural interferon-alpha (IFN-alpha) preparations, their subtype compositions, and the effects of combinations of pairs of the subtypes on virally infected cells. Our results show that the antiviral effects of these preparations depend on the target cell and on the infecting virus. The component subtypes vary with the preparations, and combinations of pairs of IFN-alpha subtypes may have synergistic or competitive effects. Our results suggest that optimal preparations of synergistically acting subtypes may provide more therapeutic benefit to patients.