Chronic pelvic pain associated with endometriosis is poorly understood. This study is an effort to better understand pelvic pain and identify novel medical approaches for treating it. Endometriosis is a very common disease of women in their reproductive years, in which endometrial tissue grows outside the uterus. In a recent epidemiologic study, we have shown strong associations among endometriosis, fibromyalgia, and autoimmune disorders. Currently, it is believed that endometriosis causes chronic pelvic pain. Yet, some women with endometriosis do not have any pain and others have pain in areas unrelated to endometriosis disease location. The standard approaches to treating endometriosis pain have been to medically alter hormone levels to prevent endometriosis tissue growth or to surgically remove endometriosis lesions. Pelvic pain is only temporarily treated by either approach, which suggests that the current classification of pain, based on disease and treatment with hormones or surgery is not adequate. The feeling of pain involves many complex processes. Generally, women suffer more frequently from chronic, long-term, painful conditions than men. This suggests that women process pain differently because of differences in sex hormone levels and genes expressed in a sexually dimorphic fashion, as well as in central nervous and immune system function differences. We will examine the relations among sex hormones, pain processing, immune system substances and pain related genes. We will also examine changes in levels of hormonal and immune substances in the blood, endometriosis lesions and normal endometrial tissue. Myofascial pain has been noted in women with endometriosis and chronic pelvic pain. We will study how the nerve, muscle and skeletal systems are involved in pelvic pain by performing an in depth pain assessment. Finally, stress plays an important role generating and perpetuating chronic pain. We will examine how the hormones related to the stress response may be altered in pelvic pain.