Introduction: There has been a recent resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Data show almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood in rats. Methods: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from Post-Natal Day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for the self-administration of nicotine vapor (PND 285-395). Plasma levels of nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session. Results: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain or sex differences detected. Adolescent nicotine exposure modestly enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG exposed females for nicotine vapor in a FR5 challenge. Conclusions: The data suggest repeated adolescent nicotine vapor inhalation leads to enhanced liability for nicotine self-administration in adulthood in female rats, but minimal change in spontaneous locomotor behavior.