Background: We have evaluated the safety and efficacy of performing endosonography-guided celiac plexus neurolysis (EUS CPN) in patients with pain due to intra-abdominal malignancies. Methods: Thirty patients with upper abdominal pain requiring narcotic analgesia and suspected or known intra-abdominal malignancy were selected for EUS CPN. This group included 25 patients with pancreas carcinoma and 5 patients with intra-abdominal metastases. Using the linear array ultrasound endoscope and a prototype needle catheter, transgastric injection of the celiac plexus with bupivacaine and 98% dehydrated absolute alcohol was accomplished. Results: Pain scores were significantly lower compared with baseline at 2, 4, 8, and 12 weeks after EUS CPN (median follow-up: 10 weeks). At these follow-up intervals, 82% to 91% of patients required the same or less pain medication and 79% to 88% of patients had persistent improvement in their pain score. Comparison of patients with TXNXM1 versus TXNXM0 pancreatic carcinoma revealed higher initial pain scores (7.9 ± 1.92 versus 5.8 ± 2.0, p = .02) and a greater decline in pain scores (decrease of 6.1 ± 3.1 versus 4.8 ± 2.0, p = .004). Complications were minor and consisted of transient diarrhea in four patients. Conclusion: EUS CPN is a safe and effective means for improving pain control in patients with intra-abdominal malignancy. The technique may be performed as an outpatient at the same setting as the EUS staging examination. (Gastrointest Endosc 1996;44:656-62.)