We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01 ), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.01). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia(P = 0.001) and are less than 38 years of age (P = 0.001). (N Engl J Med 294:1193–1199, 1976) Herpes zoster is a common infection in immunocompromised patients,123456 especially those with reticuloendothelial cancers. Because of its exaggerated course with immune suppression, herpes zoster is acutely debilitating and may even be life threatening if the viscera become involved through dissemination.5,6 The latter occurrence was assumed to be of sufficient magnitude to make herpes zoster a prime target for experimental therapeutic trials.6 In fact, until recently, even drugs known to have low therapeutic indexes (efficacy/toxicity) for the treatment of the disorder were deemed permissible candidate agents. The most notable of these agents is the purine analogue, cytarabine (cytosine arabinoside or ara-C). © 1976, Massachusetts Medical Society. All rights reserved.