Abstract Perinatal exposure to cannabinoids has been shown to elicit central nervous system impairment in rodents. This includes changes in monoaminergic and neuropeptidergic activities. We have examined the effect of perinatal exposure toΔ 9-tetrahydrocannabinol (Δ 9-THC) on sensitivity to radiant heat in both male and female rats on days 24, 50 and 70 after birth. Animals used in this experiment were born of mothers that receivedΔ 9-THC (5 mg/kg; p.o.) daily from day 5 of pregnancy until day 24 after offspring birth.Δ 9-THC perinatally treated males, but not females, showed higher baseline tail-flick values than controls on days 24 and 50 (Day 24, controls: 3.88 ± 0.18 s;Δ 9-THC group: 4.51 ± 0.18 s; Day 50, controls: 3.16 ± 0.17 s;Δ 9-THC group: 4.38 ± 0.38 s). In addition, adult males were found to be tolerant to the analgesic effect of morphine (5 mg/kg; i.p.; % analgesia: controls 71.75 ± 10.20;Δ 9-THC 35.5 ± 10.59). Moreover, recently weaned pups that received 5 mg/kg of naloxone (i.p.) developed an opioid-like withdrawal syndrome. Taken together all these results suggest that perinatal treatment withΔ 9-THC may alter the functionality of the endogenous opioid system, including changes in pain sensitivity.