Varicella, or chickenpox, is very communicable and has been shown to be transmitted to nearly 90% of household contacts. Severe varicella infections with fatal complications have been noted in children receiving corticosteroids despite the administration of varicella-zoster immune globulin (VZIG). The use of post-exposure acyclovir prophylaxis in immunocompetent children exposed to a household contact with varicella has been shown to decrease the transmission rate of varicella significantly. We studied the safety and efficacy of acyclovir prophylaxis as an adjunctive preventive measure in 8 children (10 separate exposures) receiving corticosteroids for renal disease. Four children (6 separate exposures) served as controls. No adverse reactions were reported with the acyclovir prophylaxis. The maximum change between pre- and study serum creatinine levels was 0.1 mg/dl. None of the 8 patients who received acyclovir prophylaxis developed chickenpox. One of these 8 patients developed humoral immunity to varicella despite the absence of clinical infection. One of 4 patients who received VZIG prophylaxis alone developed chickenpox. These data support the use of acyclovir prophylaxis as an adjunctive measure to VZIG for the prevention of potentially serious varicella infection in children receiving steroids.