We treated 50 patients with chronic nonmalignant pain using transdermal fentanyl (TDF) 25 mug/hr and concurrently measured pain using a visual analog scale (VAS) and serum cortisol concentration. Vile determined these outcomes at baseline and on days 30, 60, and 90 of the therapy. The patients also were asked to document any adverse effects. We found that mean cortisol concentrations on days 30, 60, and 90 of therapy were significantly (P < 0.0001) lower than the basal mean cortisol level, and mean VAS scores at days 30, 60, and 90 of therapy were also significantly better than the initial mean value (P < 0.0001). Fourteen patients experienced severe adverse events. These observations suggest that serum cortisol concentrations may be elevated. in chronic non-cancer Pain states and that TDF therapy can reduce cortisol levels, in parallel with reduction in pain. J Pain Symptom Manage 2004;28:277-281. (C) 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.