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In a double-blind study of post-cesarean analgesia, a single dose of 4 mg epidural morphine sulfate (EMS), with and without epinephrine, was compared with an equal dose of intramuscular morphine (IMS). Postoperative pain was assessed by visual analogue scores and the frequency of patient requests for subsequent meperidine injections. Plasma concentrations of morphine base after EMS and IMS were contrasted. Clinically apparent adverse effects were recorded. The stability of the preservative-free morphine preparation was substantiated. Pain indices after EMS were improved significantly over those after IMS. Pain scores and requests for intramuscular meperidine indicated that the onset of effective EMS analgesia was delayed. The duration of EMS analgesia was about 20 h. No significant difference between the effect of EMS with and without epinephrine was demonstrated. No circulatory or respiratory depression was attributed to the use of 4 mg EMS. The mean peak plasma morphine concentration after 4 mg EMS was significantly lower and later than the mean peak after 4 mg IMS. No correlation was observed between plasma morphine concentration and analgesic effect. These results support the view that epidural administration delivers more of a given dose of morphine directly (rather than via the bloodstream) to the spinal site of action than does intramuscular administration.