Acute and convalescent zoster sera taken from 11 patients with varicella and 12 patients with zoster were assayed using immunoblotting for the presence of IgG- and IgM-class antibodies to proteins present in varicella-zoster virus-infected cells. All patients exhibited a detectable virus-specific response with both antibody classes. The IgG responses involved up to 28 protein bands between 28 and 255 kilodaltons (kDa). The reactivity was particularly strong in the 78-114-kDa region, with additional bands observed with all patients at 32, 35, 66, and 220 kDa. This pattern of reactivity typically developed more slowly and was weaker and more variable in patients with varicella compared to those with zoster. The reactivity of IgM antibodies in immunoblotting was similar after varicella and after zoster. Individual sera showed up to 25 bands, with the major reactivity being directed against the 78-96-kDa region and two bands at 32 and 35 kDa. Some differences were apparent between the primary and anamnestic responses with both IgG and IgM antibodies, but this did not allow reliable discrimination of the two types of infection.