Enkephalins are a biochemical pathway for endogenous analgesia. A number of compounds inhibit degradation of enkephalins within the body. One of these compounds, D-phenylalanine (DPA), has been shown to increase the pain threshold in animals. It is hypothesized that this naloxone reversible analgesia is induced by DPA blockage of enkephalin degradation by the enzyme carboxypeptidase A. Preliminary studies of chronic pain patients have shown a response rate to DPA from 32% to 75%. This study was a double-blind crossover evaluation of a randomized parallel design to determine the efficacy of DPA in 30 subjects with chronic pain from varied etiology which was unrelieved by multiple therapeutic interventions. Each patient received a stabilized therapeutic regimen during this study consisting of four weeks of either DPA 250 mg or lactose (placebo) orally four times a day. After four weeks the DPA and placebo groups were crossed over for an additional four weeks of treatment. Pain was quantified using a visual analog pain scale and a cold pressor test. Data from the pain questionnaires revealed more pain relief on DPA reported by 25% of the patients, more pain relief on placebo reported by 22% of the patients, and no difference in pain relief reported by 53% of the patients. Lowest pain level of the visual analog scale was reported by 47% of the patients on DPA and 53% on placebo. There appears to be no significant analgesic effect from D-phenylalanine in chronic pain patients when compared to placebo.