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Varicella-zoster virus (VZV) transmission poses a major infection risk for health care workers in the hospital environment. Immunologically normal adults who contract varicella have 9 to 25 times the risk of major morbidity or death from infection compared with healthy children. Moreover, varicella infection during pregnancy is associated with a high rate of complications and the risk of the congenital varicella syndrome. To evaluate susceptibility to VZV infection among hospital workers, the employee health service screened 241 personnel for VZV antibody by the indirect fluorescent antibody technique. Overall, 7 (2.9%) of 241 personnel lacked VZV antibody and were therefore presumed susceptible to infection. Susceptibility varied dramatically by age and was significantly higher among persons 35 years of age and younger (7/93 = 7.5%) than among those aged 36 years and older (0/148 = 0%, p = 0.001). Persons 35 years old or younger with a clinical history of chickenpox or herpes zoster were much less likely to lack immunity (3/71 = 4.2%) than those stating they had no history of either (4/11 = 36.4%, p = 0.005). Screening strategies for VZV immunity in hospital employees could be made more efficient by performing serologic tests only on those persons aged 35 years or younger with a negative or uncertain history of the disease. Persons who lack antibody may be considered for preexposure immunization with live attenuated varicella vaccine as an alternative to varicella-zoster immune globulin or enforced absence from patient care after exposure to a VZV-infected patient.