Epidural injection of drug combinations may decrease toxicity by decreasing the dose of each component, but may also result in detrimental drug interactions. In this study interactions among bupivaciane, fentanyl, epinephrine, 2-chloroprocaine, and lidocaine for epidural analgesia during labor were examined. In part 1 of the study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine with 5 micrograms/ml fentanyl (n = 50), or 10 ml of this combination with 3.33 micrograms/ml freshly added epinephrine (n = 50). Epinephrine prolonged the median duration of pain relief (180 vs. 138 min, P less than 0.05) without affecting duration of first or second stages of labor, or neonatal Apgar scores. Blood pressure decreased slightly more in those receiving epinephrine, although the incidence of hypotension requiring treatment did not differ between groups. Part 2 of the study evaluated the possibility that local anesthetic used for confirming catheter tip location may interfere with the analgesic action of this bupivacaine-fentanyl-epinephrine (BFE) combination. In 50 additional parturients, a test dose of either 2-chloroprocaine (n = 25) or lidocaine (n = 25) was injected through the epidural catheter and was followed by injection of the BFE mixture. The lidocaine test dose group had a greater duration of analgesia than the 2-chloroprocaine test dose group (median duration of 164 vs. 91 min, P less than 0.05). The authors conclude that the addition of epinephrine 3.33 micrograms/ml significantly increases the duration of analgesia obtained from 0.25% bupivacaine with 5 micrograms/ml fentanyl. However, prior injection of 2-chloroprocaine, but not lidocaine, significantly decreases the duration of analgesia achieved with this BFE mixture.