Mice exposed to cold water swimming (4 degrees C) for 3 min produced a marked antinociception. Experiments were designed to determine whether pretreatment with pertussis toxin given intrathecally (i.t.) or intracerebroventricularly (i.c.v.) attenuates cold water swimming-induced antinociception in male ICR mice. Antinociception was measured by the tail-flick test 7 min after cold water swimming. I.t. pretreatment with pertussis toxin at a dose of 0.5 microgram for 24-96 h caused a time-dependent attenuation of cold water swimming-induced antinociception. Moreover, i.t. pretreatment with pertussis toxin at doses from 0.125 to 0.5 microgram for 96 h attenuated cold water swimming-induced antinociception in a dose-dependent manner. However, i.c.v. pretreatment with pertussis toxin at doses from 0.125 to 0.5 microgram for 24-96 h did not affect the cold water swimming-induced antinociception. The present results suggest that pertussis toxin-sensitive Gi/G(o) proteins in spinal cord, but not at the supraspinal sites, are involved in cold water swimming-induced antinociception.