A 32 year old white female, in apparently good health, failed to respond to conservative wound care for alveolar osteitis after a routine mandibular first molar extraction. Curettage and biopsy of necrotic alveolar bone from the #30 socket escalated her pain such that hospitalization was necessary for pain management with intravenous morphine. Twelve months prior to admission she had been placed on exogenous estrogen (Premarin, 0.625 mg/day) after a partial oophorectomy. While hospitalized, she was found to have resistance to activated protein C (APCR). Premarin was discontinued. After discharge, weekly changes of an antibiotic impregnated dressing allowed for progressive regeneration of bone and epithelium with gradual reduction in her pain. She was found to be heterozygous for the mutant Factor V Leiden, a heritable factor for increased tendency to form thrombi, so-called thrombophilia. We speculate that the exogenous estrogen administration exacerbated the thrombophilia associated with the Factor V Leiden mutation by compounding the patient's resistance to activated protein C thereby contributing to her development of osteonecrosis and severe alveolar neuralgia.