Classical conditioning in the rat fetus (Embryonic Day 20) was investi
gated in 4 experiments. Reexposure to a conditioned stimulus (CS; sucr
ose), after 3 pairings with an unconditioned stimulus (US; milk), redu
ced fetal facial wiping in a bioassay of perioral cutaneous responsive
ness. Reduced responsiveness was evident only in subjects that receive
d paired presentations of the CS and US and cannot be attributed to ha
bituation, sensitization to the CS, or protracted effects of US exposu
re during conditioning trials. Fetuses attended to the chemosensory, n
ot the tactile, qualities of the sucrose infusion during CS reexposure
. Changes in fetal responsiveness resulted from conditioned activity i
n the endogenous opioid system, specifically at mu opioid receptors. T
hese data confirm that the rat fetus is capable of exhibiting a condit
ioned opioid response in utero.