There are several interferon-alpha (IFN-alpha) subtypes. Mechanism of disparity in biological effects among members of IFN-alpha subtypes remains unexplained. Biological activity of IFN-alpha is mediated in part by induction of intracellular antiviral proteins. We studied whether differences in biologic effects of IFN-alpha subtypes may rely on their antiviral protein inducing effect. Intracellular induction of MxA protein and anti-virus-induced cytopathic effect (CPE) activity of 11 IFN-alpha subtypes in human amnion WISH cells have been studied. MxA protein quantitation in cell lysates was performed by immunochemiluminescence assay and anti-virus-induced CPE activity was assessed by protection against vesicular stomatitis virus (VSV)-induced CPE. Range of MxA values was high when cells were treated with 10 and 100 IU/ml of each IFN-alpha subtype. Levels of MxA correlated with anti-VSV-induced CPE obtained with 10 IU/ml IFN-alpha subtype. Together our data show a disparity in MxA-inducing activity of IFN-alpha subtypes and suggest that differences in anti-VSV-induced CPE of IFN-alpha subtypes in WISH cells can be related to their different ability to induce MxA.