MorphiDex, a 1:1 combination of dextromethorphan and morphine, provides satisfactory pain control at a significantly lower morphine daily dose. To determine the appropriate conversion regimens from other oral or transdermal opioid analgesics to MorphiDex (MS:DM), 592 patients with moderate to severe chronic pain requiring daily use of opioid analgesics were enrolled in this multicenter, open-label study. Patients were instructed to use MS:DM as needed to achieve satisfactory pain control. Overall, study patients took a significantly lower morphine daily dose (P = 0.0001), and a higher percentage (P = 0.0001) rated therapy with MS:DM as "very good" or "excellent" compared to their prestudy opioid. The mean daily dose of MS:DM remained level throughout a 10 month study extension period, suggesting that MS:DM may inhibit the development of tolerance to morphine. Most of the adverse events observed with MS:DM were those commonly reported with opioid therapy and were mild to moderate in severity. MS:DM appears safe and effective in treating moderate to severe chronic pain.