The objective was to determine whether deltoid as compared to gluteal injection of morphine and methadone produce differential plasma levels and analgesic effects. Thirty-two postoperative cancer patients received deltoid and gluteal injections of morphine, 8 and 16 mg, within a double-blind, twin crossover design. Forty-four patients received deltoid or gluteal methadone, 10 mg. Deltoid morphine resulted in peak plasma levels 1.8 times (P less than 0.05) those observed following gluteal morphine. Deltoid methadone resulted in peak levels 2.5 times (P less than 0.005) those following gluteal injection. Deltoid morphine resulted in an area under the drug level-time (0 to 4 hours) curve 1.4 times (N.S.) the area observed following gluteal injection. Deltoid methadone resulted in an area under the drug level-time (0 to 4 hours) curve 2.2 times (P less 0.001) the area observed following gluteal injection. Deltoid methadone, but not morphine, provided greater (1.7-fold, P less than 0.05) pain relief than gluteal injection. If more rapid and enhanced analgesia is indicated, then the deltoid site may be preferable over the gluteal site for standard doses of methadone and other lipid soluble analgesics. In addition, the relative potency of compounds of widely differing lipid solubility may depend upon the site of intramuscular injection.