Background: The new drug HP228 is a cytokine restraining agent with a broad spectrum of anti-inflammatory, analgesic, and antipyretic activity. Six healthy, adult, male volunteers were studied to determine the independent and interactive effects of HP228 and morphine on pain perception. Methods: Two groups of stimuli were applied to each volunteers before drug administration as control, 20 min after morphine and HP228 administration, and 20 min after combined administration of these two drugs. Two adhesive electrically-conducting pads were applied on opposite sides of the arm approximately 8 cm apart. The electrode were connected to an electrical impulse generator and 50 Hz 1 msec pulses of incrementally increasing intensity were delivered at 1 sec intervals. The analgesic endpoints were the current intensity (mA) at which the subject first detected the stimulus (THRESH), the intensity at which the stimulus was first idenfied as being painful (PAIN), and the intensity at which the subject requested that the stimulus be terminated due to discomfort (LIMIT). A second series of stimuli were applied immediately thereafter using 1-sec duration 50 Hz tetanus pulses with increasing intensities at 2~5 sec intervals. Results: There were significant differences between drug treatments (Morphine, HP228, HP228/Morphine) and control (No drugs) in any of the measurements (PAIN, LIMIT) except THRESH with the twitch and tetanus test. Conclusions: The data suggests that HP228 is an analgesic, but it does not appear to interact with morphine in an additive manner.