Between 1968 and 1985, 28 patients with recurrent gestational trophoblastic disease (GTD) were treated at the Southeastern Regional Trophoblastic Disease Center. Sixteen patients received primary therapy at this center and had recurrence diagnosed by re-elevation of human chorionic gonadotropin (hCG) levels after three consecutive negative levels: five (2.5%) of 204 patients with nonmetastatic GTD, three (3.7%) of 81 with good prognosis metastatic disease, and eight (13%) of 61 with poor prognosis disease. The remaining 12 patients were referred for therapy after receiving primary therapy elsewhere. All episodes of recurrence were observed within 36 months of remission with 50% and 85% before 3 and 18 months, respectively. Fourteen (56%) of 25 patients who achieved secondary remission developed a second recurrence and five (45%) of 11 surviving a second recurrence developed one or more further episodes of recurrent GTD. Nineteen patients (68%) have sustained remission 18 months following therapy for recurrent GTD. Factors relating to development and survival of recurrent disease include: poor prognosis metastatic disease, inadequate initial staging and therapy, lack of adequate maintenance chemotherapy beyond the first negative hCG level, and prolonged intervals between cycles of chemotherapy. Recent regimens introduced have contributed to an increasing salvage rate: 15 of 18 patients treated since 1978 are without evidence of disease whereas only four of ten treated prior to 1978 are currently in remission (P = 0.03).