Numerous chemotherapy regimens for treating gestational trophoblastic disease (GTD) have been described over the past 5 decades. Few studies have evaluated different chemotherapeutic agents in patients from a single center who had low-risk GTD. This retrospective review, covering the years 1980-2002, compared 3 medication regimens in 108 patients who had low-risk but persistent GTD and who received first-line chemotherapy. Forty-two patients were treated with methotrexate (MTX), 42 with dactinomycin (ACT), and 24 with a combination of MTX and ACT (MACT). Rates of complete remission were 69% in the MTX group, 61.4% in patients treated with ACT, and 79.1% in those given combination therapy. There were no significant group differences in either the duration of treatment or the number of courses of chemotherapy. Reported rates of adverse side effects were 62.5% in the MACT group, 28.6% with MTX only, and 19.1% in patients given only ACT. Grade 3 or grade 4 side effects were recorded in 2 patients in the MTX group and 2 of those given combined treatment. Hysterectomy was done in 21 patients, with no differences among treatment groups. Thirty patients required second-line chemotherapy. The investigators conclude that single-agent chemotherapy is as effective as combination chemotherapy when treating patients for low-risk GTD. Dactinomcin was the least toxic of the drugs evaluated in this study, and it might be the most cost-effective option. In areas where resources are limited, MTX-which is relatively feasible to administer-is the preferred regimen.