We investigated the analgesic effects of escalating doses (0.214, 0.286, 0.357, and 0.429 mg/kg) of oral morphine on tolerance to painful cold pressor in a double-blind, active placebo-controlled (diphenhydramine) study in 45 normal volunteers. The highest dose of morphine administered is equivalent to the starting dose recommended by the Agency for Health Care Policy and Research for the management of cancer pain and acute postoperative pain. We assessed analgesia in terms of cold pressor tolerance time and self-reported ratings of pain intensity and unpleasantness. Subjects receiving the highest dose of oral morphine showed significantly higher tolerance time than subjects receiving diphenhydramine. Neither morphine or diphenhydramine significantly reduced ratings of pain intensity and unpleasantness. Neuropsychological testing revealed that the two highest doses of morphine impaired the episodic retrieval of a word list, but the same doses did not affect motor, perceptual, or attentional tasks.