Prenatal exposure to nicotine tartrate (0.25 mg/kg/pregnant female, gestation days 3 through 21.2x daily IP) markedly decreases ambulatory activity and the number of stop and go movements in 15 day old neonatal rats. Postnatal nicotine tartrate administration alone (0.05 mg/kg SC daily from birth) does not affect these movements nor does it further the motor depression induced by prenatal nicotine treatment. Thus the critical period of neural susceptibility to nicotine appears to be during prenatal life. However, when nicotine is given both pre- and postnatally, horizontal movements are increased in the 15 day old animals, an increase that may be due to inhibition of other types of movement. These alterations in motor behavior are correlated with sharp increases in plasma ACTH levels. As our previous studies [1,25] have shown ACTH to affect neonatal motor behavior, it is suggested that nicotine-evoked ACTH release may mediate some of the motor responses attributed to the drug.