The investigation and prophylaxis with anti-varicella-zoster immunoglobulin (ZIG) of 15 preterm infants (24-33 weeks gestation and 1-300 days postnatal age) exposed to varicella on a neonatal intensive care unit are described. Varicella-zoster virus (VZV) IgG was detectable in 13 infants (24-28 weeks gestation) less than 105 days of age and born to seropositive mothers. Current guidelines recommend ZIG for all preterm infants of less than 28 weeks gestation following exposure to VZV. Our findings suggest that ZIG need be given only to seronegative infants or infants of seronegative mothers and to those over 60 days postnatal age.