The primary antiphospholipid syndrome and protein S deficiency are known hypercoagulable states predisposing to ischemic strokes. The pathogenesis of those hypercoagulable states has been independently studied and, recently, interaction between them has been proposed. A 48-year-old Hispanic man had generalized seizures 5 months after the acute onset of a left middle cerebral artery infarct. He had a strong family history of strokes. After evaluation for cardiologic, rheumatologic, hematologic and metabolic etiologies for stroke, anticardiolipin antibodies and protein S deficiency were detected. Cerebral angiography was normal. First degree relatives were evaluated and screened for these conditions. Lupus anticoagulant was detected in a sister who reported a transient hemisensory deficit. None of the relatives studied had clinical or laboratory criteria for collagen vascular diseases. Coexistence of the primary antiphospholipid syndrome and protein S deficiency, two known prothrombotic states, has rarely been reported in Hispanic adults in association with ischemic stroke.