The course of 51 patients with high-risk metastatic gestational trophoblastic tumor was reviewed. The clinical characteristics and therapy of patients who died were compared to patients who attained remission to identify parameters that are associated with treatment failure. The presence of liver, brain, or intestinal metastases and the failure of prior chemotherapy were found to portend a poor prognosis (P less than 0.001, P less than 0.05). Other high-risk factors such as markedly elevated HCG levels, time interval greater than 4 months from the antecedent pregnancy to treatment, and post-term choriocarcinoma were not independently associated with treatment failure. The mean prognostic score and the mean number of high-risk factors for patients who died were 13 and 3, as compared to 7 and 2, respectively, for patients who achieved remission (P less than 0.001, P less than 0.001). Alternative intensive chemotherapy regimens need to be developed to improve remission rates in patients with liver, brain, or intestinal metastases, failed prior chemotherapy, or a high prognostic score.