The serological response of patients with acute herpes zoster was studied to determine whether a diagnosis could be made on a single serum sample, and whether this response was modified by treatment with antiviral and/or steroid therapy. The patients received one of four regimes of acyclovir and prednisolone, Varicella zoster virus (VZV) IgG, IgM, and IgA responses were measured by commercial and in-house enzyme immunoassays (EIA) using serum samples taken at days 0, 7, and 21 after entry into the study. Samples were also tested for IgM to Epstein-Barr virus (EBV) viral capsid antigen (VCA), and cytomegalovirus (CMV) IgM and for herpes simplex virus (HSV) antibodies by the complement fixation test (CFT). Analysis was carried out on data from 71 patients. VZV IgM was detected in 72%, VZV IgA in 78%, and either VZV IgM or IgA in 88% of patients tested, at some time during the 3-week study period. The optimal time to detect either class of antibody was approximately 1 week after the onset of the vesicular rash, when 85% of patients had one or both classes of acute phase antibody in their serum. There was no evidence of cross reaction with EBV, CMV, or HSV antibodies. Neither treatment with prednisolone nor the length of therapy with acyclovir affected significantly the VZV IgM or IgA responses. Therefore it is possible to make a serological diagnosis of herpes zoster on a single sample, optimally 1 week after the onset of the rash, in patients treated with acyclovir alone or with acyclovir and steroids.