Reactivation of varicella herpes virus (VHV) latent in individuals who have previously suffered varicella, gives rise to herpes zoster and in some cases leads to a sequela of post herpetic neuritis with severe pain which is refractory to analgesics. Many different antiviral agents have been tried without achieving satisfactory results. Of all the antiviral agents employed, acyclovir has been the most successful in reducing post herpetic pain. However acyclovir has not been as reliable as interferon α(IFN-α). We have previously looked into the use of transfer factor (TF) as a modulator of the immune system, specifically with respect to its effectiveness in the treatment of herpes zoster. In this work findings from a comparative clinical evaluation are presented. A double blind clinical trial of TF vs acyclovir was carried out in which 28 patients, presenting acute stage herpes zoster, were randomly assigned to either treatment group. Treatment was administered for seven days and the patients were subsequently submitted to daily clinical observation for an additional 14 days. An analogue visual scale was implemented in order to record pain and thereby served as the clinical parameter for scoring results. The group treated with TF was found to have a more favorable clinical course, P≤0.015. Laboratory tests to assess the immune profile of the patients were performed two days prior and 14 days after initial treatment. The results of these tests showed an increase in IFN-γ levels, augmentation in the CD4+ cell population but not the percentage of T rosettes in the TF treated group. These parameters were however insignificantly modified in patients receiving acyclovir. Although TF treated patients showed an increase in CD4+ counts these cells remained below the levels for healthy individuals. The fact that IFN-γ levels as wells as the counts for CD4+ cells rose in the TF treated group and not in theacyclovir one is very signi_cant and con_rms the immunomodulating properties of TF. (C) 1998 International Society for Immunopharmacology. Published by Elsevier Science Ltd.