The varicella-zoster virus (VZV) membrane glycoprotein gpI elicits a major immunoglobulin G antibody response after naturally acquired VZV infection; antibody to a nonglycosylated immediate-early protein, IE-62 (p170), represents a response to a nonmembrane VZV component. We evaluated antibody response to VZV gpI and IE-62 (p170) at 28 days and 1 year following infection in 34 children (ages 5 to 16 years) enrolled in a randomized placebo-controlled study of oral acyclovir for the treatment of varicella. All children were VZV antibody negative at enrollment, were previously healthy and had laboratory-documented varicella. Compared with placebo recipients, acyclovir recipients had lower geometric mean titers by the fluorescent antibody to membrane antigen technique at 28 days (620 versus 836) but similar titers at 1 year (122 versus 122). All children had antibodies to gpI and IE-62 detectable by enzyme-linked immunosorbent assay at 28 days and 1 year. No difference in gpI at 28 days compared with 1 year was noted in acyclovir recipients. No difference in antibody to IE-62 (p170) was noted when acyclovir and placebo recipients were compared at either 28 days or 1 year. Antibody responses to gpI and IE were similar when children were stratified by age (5 to 6 years, 7 to 11 years, 12 to 16 years). A short course of oral acyclovir for the treatment of varicella did not affect antibody responses to gpI or IE-62 (p170) in healthy children at 28 days and 1 year following varicella.