The antinociceptive and locomotor effects of microinjecting morphine into the rostral ventromedial medulla (RVM) of male and female rats was assessed. Male rats showed greater antinociception than female rats at all doses and times following morphine administration. Male, but not female rats, also showed a dose dependent decrease in locomotion. These data demonstrate that sex differences in antinociception are mediated at least in part by the RVM.