The effects of neonatal hormone manipulations on swim stress-induced analgesia (SSIA) magnitude and neurochemical quality were examined in Swiss-Webster mice of both sexes. Previous research has indicated that non-opioid SSIA mechanisms in adult Swiss-Webster mice are sexually dimorphic. Male mice exhibit non-opioid SSIA following a 3-min swim in cold (15 degrees C) water that is antagonized by the non-competitive NMDA antagonist MK-801 (dizocilpine; 0.075 mg/kg), whereas female mice do not display NMDA-mediated analgesia in the presence of estrogen. Since male and female mice show equipotent magnitudes of SSIA, it was concluded that female mice display a neurochemically distinct, estrogen-dependent SSIA mechanism specific to their gender. In the present study, female mice exposed to testosterone during the neonatal period display NMDA-mediated analgesia even in the presence of estrogen in adulthood. Thus, expression of the female-specific, estrogen-dependent SSIA mechanism previously described may be dependent on the absence of testosterone during early ontogeny.