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Strains of varicella-zoster virus resistant to 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) were isolated from varicella-zoster virus-infected Vero cells which were pulse-treated with 5-iododeoxyuridine or 5-bromodeoxyuridine or both and then treated with BV-araU. These BV-araU-resistant strains (BV-araUr) could not be isolated from varicella-zoster virus-infected cells treated with BV-araU alone and had reduced viral thymidine kinase activity. Two of five BV-araUr strains were also resistant to 5-iododeoxyuridine and 5-bromodeoxyuridine, whereas other BV-araUr strains were relatively susceptible to these drugs. All clones from the BV-araUr strain were susceptible to 1-beta-D-arabinofuranosylcytosine and phosphonoacetic acid, but 7 of 10 clones from the BV-araUr strain were resistant to 1-beta-D-arabinofuranosyladenine. The possible mechanisms of induction of BV-araU resistance are discussed.