The choice between morphine and meperidine for postoperative pain is usually based on the preference of the prescriber, as few objective comparative data are available. This blind, randomized study compared the efficacy and side effects of morphine and meperidine administered by patient-controlled analgesia (PCA) for postoperative pain. One hundred two consenting patients scheduled for major abdominal surgery were randomly assigned to receive PCA with morphine (0.75, 1.0, or 1.5 mg bolus dose size) or meperidine (9, 12, or 18 mg) for pain control. Postoperative assessments included pain at rest and on sitting, nausea, unusual dreams, the Multiple Affect Adjective Check List (a measure of mood), and the trailmaking tests A and B (measures of ability to concentrate). Pain on sitting (P = 0.037) but not pain at rest (P = 0.8) was significantly less in patients receiving morphine. Meperidine use was associated with poorer performance in the trailmaking tests and a greater incidence of dryness of the mouth. Severity of nausea, mood, and incidence of unusual dreams did not differ significantly between drugs. We conclude that meperidine should be reserved for those patients in whom morphine is judged inappropriate.