A retrospective study of sequential obstetric patients delivering at University Hospital and receiving epidural anesthesia was conducted to determine if a suggested association exists between the recurrence of oral herpes simplex lesions and the use of epidural morphine. In a retrospective study of 291 patients, 13 of 134 (9.7%) receiving epidural morphine developed recurrent oral herpes lesions in contrast to 1 of 157 (0.6%) not receiving the drug (P less than 0.001). In a prospective hospital-based study of 729 consecutive obstetric patients, 146 patients received epidural opioids (morphine, fentanyl, or both) and 583 did not. Recurrent HSVL lesions occurred in 13 of 140 (9.3%) patients given epidural morphine but in only 6 of 583 (1.0%) not given epidural opioids (P less than 0.001). Three of the 13 patients with HSVL received both epidural morphine and fentanyl and 10 received only epidural morphine. Because of the small numbers of patients receiving only fentanyl, no relation between HSVL reactivation and epidural fentanyl could be established. In patients having caesarean sections, the association of recurrent HSVL and the use of epidural morphine was significant (P = 0.04), suggesting cesarean delivery was not a confounder. A hitherto undescribed triggering agent, epidural morphine, appears to be associated with reactivation of HSVL in obstetric patients in the postpartum period.