Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E[subscript 2] treatment followed by 2 d of vehicle treatment, or were injected with E[subscript 2] daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E[subscript 2] levels during conditioning did not affect subsequent CPP expression. During extinction, daily E[subscript 2] administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E[subscript 2]-treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E[subscript 2] could rescue extinction in these rats, half were given daily E[subscript 2] treatment and half were given vehicle. E[subscript 2]-treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E[subscript 2] is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E[subscript 2] levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.