BACKGROUND: Recombinant activated factor VII (rFVIIa) is being tested to improve hemostasis in a variety of bleeding disorders. Clinical indications and efficacy are still being evaluated for this product. CASE REPORT: Over a 17-month period, rFVIIa was used to treat central nervous system hemorrhage in three patients who were found to have isolated FVII deficiency (21%, 40%, 27%). Patient A fell 30 feet, Patient B suffered a motor vehicle accident, and Patient C had a spinal cord hematoma. None of the patients had a history of bleeding diathesis. All three patients received rFVIIa after failing initial treatment with fresh-frozen plasma. RESULTS: Patient A was treated with 11 doses (initial dose 95 microg/kg; subsequent doses 8-38 microg/kg) over 10 days; Patient B received 13 doses (45-60 microg/kg) over 13 days; and Patient C received 5 doses (12-24 microg/kg) over 4 days. The prothrombin time corrected from 16.2 +/- 1.8 (mean +/- SD) to 11.2 +/- 1.6 seconds after infusion of rFVIIa, but returned to pretreatment level in 14 +/- 4 hours. At the cessation of therapy, all patients showed neurologic improvement. No complications related to the infusion of rFVIIa occurred. CONCLUSION: The use of rFVIIa may be of value both for its general effect on hemostasis, and specifically in the setting where there is a documented reduction in FVII. Doses lower than those used in patients with FVIII inhibitors appear to be effective in the setting of central nervous system hemorrhage.