In order to assess further the clinical usefulness of vidarabine therapy of chicken pox, a double-blind, placebo-controlled trial was performed in immunocompromised patients. Thirty-four patients entered the trial; 19 received vidarabine and 15 the placebo. All patients had disease≤72 hours in duration and 23 had lymphoproliferative malignancies. Both patient populations were balanced for underlying disease, preceding chemotherapy, and duration of chicken pox. No patient received zoster immune globulin. Drug therapy accelerated cessation of new vesicle formation (P=0.015) and decreased median daily lesion counts (P=0.06 on days 2 and 3). Fever (≥37.8°C orally) resolved more rapidly in the drug-treated group. By day five, 70% of drug-treated subjects were afebrile in contrast to 35% of placebo recipients (P=0.066). One drug recipient developed mild pneumonitis during the study which resolved with therapy, whereas eight placebo recipients developed varicella-related complications which led to death in two patients (P<0.01). These results were achieved with minimal evidence of laboratory or clinical toxicity related to drug administration. The findings indicate that vidarabine has a good therapeutic index (efficacy/toxicity) for treatment of chicken pox in immunocompromised patients when given early in the course of the infection. © 1982 The C. V. Mosby Company.