The authors report the first American case of a factor VIII inhibitor found in a patient with Sjogren's syndrome. The inhibitor was isolated from a patient with no known hematologic disorder who was seen with a compartment syndrome of the left thigh after sustaining a fall from bed. The Sjogren's syndrome had been previously diagnosed via lower lip biopsy. After fasciotomy, signs and symptoms of intra-abdominal hemorrhage developed, and the patient was taken to laparotomy, where no hemorrhage was found. A coagulopathy developed, and the patient's hemoglobin continued to fall. A complete factor analysis revealed a factor VIII inhibitor that was quantified at 40 Bethesda units. After vigorous therapy--which included factor concentrates, immunoglobulins, steroids, antifibrinolytic agents, and blood replacement--the patient's bleeding stopped and she continued to convalesce under hospital care until her ultimate death from respiratory problems. Acquired hemophilia with a factor VIII inhibitor may be associated with Sjogren's syndrome.