Varicella-zoster virus (VZV), one of the most common highly communicable agents of disease, stimulates aggressive infection control measures. In a 1-year period, at one hospital, at least 93 inpatients (82 adult patients, 11 pediatric patients) and 2 hospital staff with active varicella-zoster infections served as potential sources of nosocomial infection. Six incidents of exposure to the virus that occurred without the protection of standard infection control precautions were investigated by the infection control surveillance team. One hundred fifty-six patients and 353 hospital staff were exposed. Fifty-one patients had no history of varicella-zoster infection, but only five were susceptible by serologic testing. One hundred one staff members had no history of varicella-zoster, but only 11 were susceptible by serologic testing. These exposures resulted in three secondary varicella-zoster infections, six courses of varicella-zoster immune globulin prophylaxis and furlough of 13 staff members. Epidemiologic investigation consumed approximately 356 hours of staff time, and management of exposed persons cost approximately $41,500. Prospective knowledge of the immune status of health care workers would vastly decrease the time and effort required to control hospital VZV exposures.