 Cocaine dependence is a chronic, relapsing disorder in which stressnegative mood and exposure to drug-related stimuli or cues are associated with high rates of relapse McKay et al., 1995; OBrien et al., 1998; R. Sinha, 2001; Shaham et al., 2003. In particular, sex differences in relapse precipitants have been noted, with women reporting greater stress related relapses while men report higher number of relapses associated with drug cuetemptation situations Lex, 1991; McKay et al., 1996; R. Sinha, 2001; R. Sinha, Rounsaville BJ, 2002. Current SCOR studies have shown that stress and cocaine cues increase drug craving and stress related arousal, responses that differ in cocaine men and women R. Sinha et al., 2003; H.C. Fox et al., 2005a. Furthermore, stress-induced cocaine craving and HPA responses are predictive of cocaine relapse, which is also moderated by gender R. Sinha et al., 2006. However, no previous research has examined the basis of sex differences in stress and cue induced craving and arousal, both of which are known to increase relapse susceptibility. Greater knowledge of the sex-specific neurobiology of cocaine dependence will facilitate development of gender-specific cocaine relapse prevention efforts. 