Although acyclovir is prescribed to women of reproductive age, no information currently exists regarding the advisability of its use in lactating women. This report documents the first known case of acyclovir transfer to an infant through breast milk. Maternal plasma, milk, and infant urine were collected following a 200-mg oral dose of acyclovir. The drug concentration in breast milk exceeded the corresponding plasma concentration except at the time of peak plasma concentration. This would not be expected on the basis of simple diffusion, and might be caused by a facilitated or active transport mechanism. Such a mechanism has not been described for any drug in human breast milk. Subtherapeutic amounts of acyclovir were documented in the infant, and we discuss the potential effects on neonatal immune function. The use of acyclovir in lactating women remains controversial until further study can clarify pertinent questions.