We report stroke in a 62-year-old woman who had been on hormone replacement therapy (HRT), estrogen plus progestin, for more than 8 years. She experienced two episodes of transient ischemic attack (TIA), manifesting as right-sided weakness, that persisted for 10-20 min. Magnetic resonance angiography (MRA) obtained before complete stroke, demonstrated severe stenosis of the left middle cerebral artery, without evidence of cerebral infarction. Twenty days after the TIA she suffered a complete stroke corresponding with the site of stenosis. Her protein S activity was low 29%. In the context of the recent findings of the US Women's Health Initiative, we concur that the safety of long-term HRT should be considered carefully, especially in women with a history of TIA and confirmed cerebral artery stenosis.