A dosage of 1 g of valacyclovir 3 times per day (TID) for 7 days has already been shown to be superior to an oral dosage of 800 mg acyclovir 5 times per day for 7 days in immunocompetent individuals. The objective of this study was to assess the safety and efficacy of an oral dosage of valacyclovir, 1 g TID versus 2 g TID, for the treatment of herpes zoster in immunocompromised patients > or =18 years of age. The oral dosage schedule of 2 g of valacyclovir TID reaches acyclovir plasma levels similar to those achieved with intravenous acyclovir therapy given to immunocompromised patients (10 mg/kg every 8 h for 7 days). In this double-blind study, 87 immunocompromised patients with clinical evidence of localized herpes zoster were randomized to receive oral valacyclovir therapy for 7 days, either 1 g TID or 2 g TID, within 72 h after onset of zoster rash. Patients were seen and assessed for cutaneous healing, zoster-associated pain (ZAP), and/or zoster-associated abnormal sensations (ZAAS), up to 24 weeks. Participants in both arms of the study demonstrated similar median times to full crusting of the rash (8 days), and both dosages were safe and effective therapies for reduction of ZAP and ZAAS in the immunocompromised patient population.