OBJECTIVE To study the clinical course of varicella-zoster infection in children infected with human immunodeficiency virus type I. METHODS A clinical and laboratory study of human immunodeficiency virus-infected children was undertaken at Cedars-Sinai Medical Center, Los Angeles. METHODS Twenty-seven human immunodeficiency virus-infected children aged 1 to 13 years who were treated between 1987 and 1992. Twenty-one children had acquired the infection through blood transfusion, 18 during the neonatal period and three during their early years of life. Six infants had acquired the infection perinatally. RESULTS Seventeen children have developed varicella, of whom 10 had an uncomplicated course and seven suffered from chronic, recurrent, or persistent varicella. Uncomplicated or recurrent varicella was a relatively benign illness that did not require antiviral therapy except in one child. In contrast, patients with persistent varicella required antiviral therapy as they were sicker and had a prolonged course. One had pneumonia, and another patient developed hyperkeratotic lesions that were refractory to therapy. They had lower CD4 counts (P < .01) and had a more advanced stage of the human immunodeficiency virus disease than the other children. Three patients who were receiving regular intravenous immunoglobulin developed their initial attack of varicella despite the presence of the varicella-zoster antibody. Four patients, three of whom had uncomplicated varicella, developed zoster involving one or two dermatomes. One patient developed zoster while receiving acyclovir therapy. CONCLUSIONS Children infected with human immunodeficiency virus type 1 may suffer unusual manifestations of varicella-zoster infection. The incidence of zoster in these children is higher than in the general population and is close to that in patients with leukemia. The effectiveness of antiviral therapy in these patients was difficult to evaluate.