To determine accurately the central analgesic effects of opioid peptides, we devised a special technique for intracisternal administration of drugs to conscious mice. When this method was utilized we found that a series of endogenous opioid peptides and enkephalin analogues, (D-Ala 2, Met 5)-enkephalinamide and (D-Met 2,Pro 5)-enkephalinamide produced dose-related analgesic effects, as determined by the tail pinch test. These effects were antagonized by pretreatment with naloxone 0.5 mg/kg s.c. This technique should be a most accurate one for the determination of central analgesic effects of various drugs in conscious mice.