A highly sensitive indirect fluorescence antibody test (IFAT) has been developed on the basis of varicella-zoster virus (VZV)-infected human lung carcinoma (A549) cells and evaluated for the determination of immunity to VZV. Different serum panels with negative, low, moderate or high anti-VZV IgG levels detected by the fluorescent antibody to membrane antigen (FAMA) assay were investigated. As a result, the sensitivity and the specificity of IFAT were 100% compared to FAMA test. In anti-VZV IgG-positive sera, a significant correlation between the results of FAMA procedure and IFAT could be shown. However, there were considerably higher antibody titers by the IFAT than by FAMA. Whereas the FAMA test had a detection limit of 250 mIU/ml anti-VZV IgG, the limit of detection of IFAT was 50 mIU/ml. In conclusion, the IFAT using VZV-infected A549 cells as antigen allows a highly sensitive, specific, and rapid detection of anti-VZV IgG class antibodies. This simple technique can replace the labor-intensive FAMA procedure for laboratory determination of immunity to VZV.