Iontophoresis is a method of transdermal administration of ionized drugs in which electrically charged molecules are propelled through the skin by an external electrical field. This was a prospective, randomized, single-blind study to determine the effectiveness of iontophoretically delivered morphine HCl for the control of postoperative pain. Thirty-eight patients who underwent total knee or hip replacement completed this clinical trial. Informed consent was obtained before surgery and patients were instructed on the use of a patient-controlled analgesia (PCA) device. Postoperatively, pain in the recovery room was initially controlled with IV meperidine, and thereafter with PCA therapy using meperidine, 2 mg/cc, with a dose of 10 mg IV and a lock-out period of 15 min. The dose was adjusted as necessary and the lock-out period remained the same. The number of patient requests and the dose (mg) administered was recorded hourly. On the morning following surgery, iontophoresis devices were attached for 6 hr to patients who received either morphine HCl or lactated ringers solution. During this period and for 12 hr following completion of iontophoresis, PCA analgesia remained available to patients. Venous blood samples for determination of morphine levels were obtained every 30 min during iontophoresis, then every 60 min for 2 hr following iontophoresis. Of the 38 patients, 17 received iontophoresed morphine, and 21 received iontophoresed lactated ringers. The morphine group utilized the PCA device more than the control group during the baseline period. However, following the institution of iontophoresis and continuing up to 12 hr following completion of iontophoresis, the morphine group used significantly less PCA meperidine to maintain analgesia than the control group (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)