In a prospective study, third trimester plasma levels of BE and ACTH were determined in 58 women who delivered vaginally. Peptide regulation was compared between subjects who used conduction anesthesia at delivery and subjects who did not. Third trimester levels of maternal BE and ACTH were significantly related; however, the relationship was significant only in subjects who did not receive conduction anesthesia (n = 24) at delivery. The normal co-release pattern between BE and ACTH in subjects receiving conduction anesthesia (n = 34) during birth was uncoupled. The use of conduction analgesia during vaginal delivery was significantly related to a disregulation index created to quantify the BE-ACTH release pattern. Uncoupled ACTH and BE patterns may result from modified control of pro-opiomelanocortin (POMC) expression during pregnancy or unique proteolytic processing of POMC, and may alter pain tolerance during delivery.