Thirty-two patients with chronic pain due to advanced cancer were treated with methylphenidate (10 mg with breakfast and 5 mg with lunch) for 3 days, versus placebo, in a randomized, double-blind, cross-over study designed to evaluate the capacity of methylphenidate to potentiate the analgesic effect of narcotics and/or to decrease sedation induced by narcotics. In 28 evaluable patients, the intensity of pain (visual analogue 0-100) and intake of extra doses of analgesics (number of doses/day) were 43 +/- 27 and 2.2 +/- 2.4 during methylphenidate, versus 55 +/- 24 (P less than 0.02) and 2.9 +/- 2.9 (P less than 0.002) during placebo, respectively. Activity and drowsiness (visual analogue 0-100) were 57 +/- 25 and 58 +/- 24 after methylphenidate, respectively, versus 41 +/- 26 (P less than 0.05) and 45 +/- 27 (P less than 0.02) after placebo. Upon completion of the study, the investigator and the patient chose methylphenidate blindly as a more useful drug in 23 cases (83%) and 20 cases (70%), respectively (P less than 0.02). No cases of severe toxicity were observed. We conclude that methylphenidate can increase the analgesic effect and decrease sedation of narcotics in this population.