Emerging research in animal models and healthy women indicates that the sex hormone estradiol may moderate fear of extinction. There is limited research on estradiol in exposure-based therapy among clinically anxious women. The current pilot study aimed to address this gap by comparing exposure outcomes in women with panic disorder (PD) who had high (HE) vs. low estradiol (LE). Twenty-eight women (14 per group) with PD completed two interoceptive exposure sessions on consecutive days as well as self-report measures of panic severity. Electrodermal activity was assessed continuously throughout the exposure sessions. Results showed that although anxiety sensitivity and subjective distress improved from pre- to postexposure, suggesting that the intervention was effective in reducing panic-related anxiety, there were no differences in outcomes between the HE and LE groups. The findings suggest that estradiol may not moderate outcomes in exposure therapy in clinically anxious samples, although replication in larger samples will be needed.