alpha-d-Propoxyphene and its principle metabolite, alpha-d-norpropoxyphene, were compared pharmacologically to establish their relative opioid profiles as defined by naloxone reversal. Propoxyphene exhibited opioid activity in the following tests: mouse abdominal constriction and rat tail heat analgesic tests, inhibition of the twitch of the guinea-pig ileum and acute lethality in rodents. Norpropoxyphene also showed opioid activity in the rat tail heat and guinea-pig ileum tests, but exhibited nonopioid activity in the mouse abdominal constriction and acute toxicity studies. Jumping in mice, precipitated by naloxone, suggests the following order for liability to produce physical dependence after repeated administration: morphine greater than codeine greater than propoxyphene greater than norpropoxyphene approximately saline. Propoxyphene and norpropoxyphene depressed axonal conduction in isolated peripheral nerve and were comparable in potency to standard local anesthetic agents. The nonopioid actions of norpropoxyphene might be due in part to its local anesthetic properties.