The effects of intrathecal (i.t.) and intracerebroventricular (i.c.v.) treatments with galanin on inhibition of the tail-flick and paw-licking hot-plate responses induced by beta-endorphin and morphine administered i.c.v. were studied in ICR mice. Galanin (100 ng) given i.t. effectively antagonized inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin (1 microgram) but not morphine (1 microgram). However, the same dose of galanin given i.t. did not affect inhibition of the hot-plate response induced by beta-endorphin and morphine administered i.c.v. Intrathecal treatment with various doses of galanin (0.1-100 ng) dose-dependently antagonized the inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. Galanin (100 ng) in combination with beta-endorphin (1 microgram) or morphine (1 microgram) given i.c.v. did not affect beta-endorphin- or morphine-induced inhibition of the tail-flick and hot-plate responses. It is concluded that galanin given i.t. selectively attenuates i.c.v. beta-endorphin-induced inhibition of the tail-flick response by inhibiting descending epsilon-opioid system activated by supraspinally applied beta-endorphin.