Persistent gestational trophoblastic disease is potentially fatal, but the majority of patients are cured with chemotherapy. Any developments in treatment are therefore being directed towards maintaining efficacy and reducing toxicity. We evaluated efficacy and toxicity of methotrexate, etoposide and dactinomycin (MEA) as first-line therapy for high risk disease and etoposide and dactinomycin (EA) as second-line therapy for methotrexate-refractory low risk disease in a retrospective analysis of 73 patients (38 MEA, 35 EA) treated since 1986 at a supra-regional centre. The median follow-up period was 5.5 years and the median number of cycles received was 7. The overall complete response rate was 85% (97% for EA, 75% for MEA). Of eight patients who failed to respond, four have since died and four were cured with platinum-based chemotherapy. Alopecia was universal. Grade II or worse nausea, emesis, or stomatitis was observed in 29%, 30% and 37% respectively. Fifty-one per cent experienced grade II/III anaemia, 8% grade II or higher thrombocytopenia and 64% grade III or IV neutropenia; in six cases this was complicated by sepsis. Fifty-four per cent of patients went on to have a normal pregnancy. No patient has developed a second malignancy. In conclusion, the MEA and EA chemotherapy regimens for persistent trophoblastic disease are very well tolerated, do not appear to affect future fertility and are associated with excellent, sustained complete response rates.