Transmucosal fentanyl (TF) has recently become available for treatment of breakthrough pain in cancer patients who are already tolerant to opioids. In addition to cancer patients, there is a growing number of chronic pain patients who regularly use and are tolerant to opioids and require a breakthrough opioid for adequate pain control. This pilot study was done to determine if TF is effective and acceptable to non-malignant, chronic pain patients who are opioid tolerant and require a breakthrough opioid(s) for pain control. Sixty patients with chronic, non-malignant pain who were maintained on a long-acting opioid and who required breakthrough pain control were given TF in an initial dose of 400 or 600 mcg per single, transmuscosal administration. Among the study group 35 (58.3%) experienced chronic pain due to injuries to the spine and 25 (41.7%) were due to medical conditions other than cancer. After at least three months of usage, patients were asked if they desired to continue TF and the reason(s) why they believed it to be effective. Fifty-eight (96.7%) of these subjects perceived that TF was an effective breakthrough opioid and desired to continue it. The single, effective dosage ranged from 800 to 1600 mcg per administration, and the number of separate monthly dosages ranged from 2 to 360. The majority of patients used TF only for emergency, pain purposes but others preferred TF as their major breakthrough opioid and ceased use of other short-acting opioids including injectable meperidine. Reported reasons for widespread patient acceptance included TF's fast action, fewer bed-bound days, increased energy, decreased use of other opioids, less depression, and fewer emergency room visits. This pilot study indicates that TF is effective and desired as a preferential opioid for breakthrough pain by a high percentage of chronic, non-malignant pain patients.