No studies have been reported previously on fetal behavior after chronic morphine administration during the period of opiate receptor ontogenesis. In the present study, pregnant rats were injected with 20 mg/kg/day divided into either two or four daily doses. The injections were made from day 12 through the end of gestation. On days 18-20, the effect of morphine and naloxone on fetal activity in the pretreated animals was assessed by visual observation and quantification. Animals exposed twice daily to morphine showed a morphine-induced depression in spontaneous activity similar to animals pretreated with saline while animals injected four times daily developed tolerance to the depressant effect of the morphine. Animals injected with either morphine or levorphanol were hyperactive after challenge with naloxone. Animals injected with saline or dextrorphan or pair-fed were not hyperactive after exposure to naloxone. Even though behavioral changes were seen in utero after injection of morphine, 30-day neonates which had been treated identically prenatally did not show changes in the analgesic response to morphine.