Although most patients with cancer-related pain obtain relief with available therapies, swallowing difficulties or intestinal obstruction preclude oral analgesic delivery. Topical morphine may provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. Therefore, we conducted a randomized, placebo controlled, double-blind, crossover study of five healthy volunteers after they provided institutionally approved written informed consent. They were admitted to the General Clinical Research Center (GCRC) of Northwestern University twice, being randomly assigned to receive either one mL of morphine compounded at 10 mg/mL in pluronic lecithin organogel (PLO) base (ExcelleRx, Philadelphia, PA) applied to the wrist and one mL of normal saline administered subcutaneously or one mL of topical drug-free PLO base and one mL of subcutaneous morphine 3 mg/mL on the first occasion and the opposite combination on the second occasion. Seventeen blood samples were collected from 5 min to 10 h after dose administration for determination of plasma morphine concentrations. Plasma samples were prepared by solid-phase extraction and morphine concentrations measure by an LC-MS-MS technique with a linear range of 0.5 – 500 ng/ml. Bioavailability of the topical formulation was estimated from doses and areas under the curves, assuming the subcutaneous dose bioavailability was 100%. The median bioavailability of morphine compounded in a PLO base and administered topically to volunteers was less than 2%. Despite a report that topical morphine is effective in controlling chronic arthritis pain, the present results are consistent with the report that morphine was minimally absorbed transdermally from a PLO formulation in dogs. These results suggest that transdermal administration of morphine compounded in a PLO base is unlikely to provide relief of cancer-related pain. Supported in part by a grant from ExcelleRx. Although most patients with cancer-related pain obtain relief with available therapies, swallowing difficulties or intestinal obstruction preclude oral analgesic delivery. Topical morphine may provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. Therefore, we conducted a randomized, placebo controlled, double-blind, crossover study of five healthy volunteers after they provided institutionally approved written informed consent. They were admitted to the General Clinical Research Center (GCRC) of Northwestern University twice, being randomly assigned to receive either one mL of morphine compounded at 10 mg/mL in pluronic lecithin organogel (PLO) base (ExcelleRx, Philadelphia, PA) applied to the wrist and one mL of normal saline administered subcutaneously or one mL of topical drug-free PLO base and one mL of subcutaneous morphine 3 mg/mL on the first occasion and the opposite combination on the second occasion. Seventeen blood samples were collected from 5 min to 10 h after dose administration for determination of plasma morphine concentrations. Plasma samples were prepared by solid-phase extraction and morphine concentrations measure by an LC-MS-MS technique with a linear range of 0.5 – 500 ng/ml. Bioavailability of the topical formulation was estimated from doses and areas under the curves, assuming the subcutaneous dose bioavailability was 100%. The median bioavailability of morphine compounded in a PLO base and administered topically to volunteers was less than 2%. Despite a report that topical morphine is effective in controlling chronic arthritis pain, the present results are consistent with the report that morphine was minimally absorbed transdermally from a PLO formulation in dogs. These results suggest that transdermal administration of morphine compounded in a PLO base is unlikely to provide relief of cancer-related pain. Supported in part by a grant from ExcelleRx.