The possible analgesic effects of i.c.v. administration of several aminoglycoside antibiotics were evaluated in mice using hot plate and tail flick tests. Neomycin (10-80 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80-320 micrograms/mouse) produced dose-dependent increases in the latencies to forepaw licking and jumping in hot plate test. These drugs also produced dose-dependent increases in the percentage of animals showing analgesia in tail flick test. The order of potency of these aminoglycoside antibiotics in both tests was neomycin greater than gentamicin greater than kanamycin, which is exactly the same order that these drugs show as N-type calcium channel blockers. Bearing in mind this fact and the well known analgesic activity of several drugs which decrease neuronal calcium availability, we suggest that the mechanism of aminoglycoside-induced antinociception may be related to the capacity of these antibiotics to block N-type calcium channels and decrease neuronal calcium availability.