Evidence is presented to show a strong and long-lasting analgesic effect after injection of dynorphin into the subarachnoid space of the spinal cord of the rat. Calculating on a molar basis dynorphin was 6-10 times more potent than morphine and 65-100 times more potent than morphiceptin, the specific mu receptor agonist. Dynorphin analgesia was completely reversed by intrathecal injection of anti-dynorphin IgG and partially reversed by naloxone. Acute tolerance to morphine analgesia did not affect the occurrence of dynorphin analgesia. Evidence from different lines of approach suggest that dynorphin may bind with kappa receptors in the spinal cord to exert its analgesic effect.