The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < 0.001). Intrathecal morphine was also reduced by 1-5 mg/day. Nimodipine was withdrawn in 5 patients during the first week of treatment due to intolerance (n = 3) or aggravation of the disease (n = 2). These preliminary results support experimental findings showing that pharmacological interference with Ca(2+)-related events may modify chronic opioid effects, including the expression of tolerance.