The Gynecologic Oncology Group (GOG) conducted a prospective trial of single-dose Actinomycin-D (ACT-D) given intravenously (IV) at 1.25 mg/m2 every 2 weeks to patients with nonmetastatic gestational trophoblastic disease (NMGTD) in order to determine the efficacy of pulse scheduling and the frequency and severity of associated toxicity. Of 31 evaluable patients, 29 (94%) achieved remission after receiving a median of four courses of therapy. Two patients who failed to respond to pulse therapy were subsequently cured by alternative treatment. There were 93 toxic events in 133 cycles of therapy. Ninety-two percent of adverse effects were graded as mild or moderate, and 8% were graded as severe. No life-threatening toxicity occurred. Although single-dose ACT-D efficacy and toxicity is comparable to conventional therapy for NMGTD, the advantages of easier administration, greater patient convenience, and improved cost-effectiveness make it superior to other alternatives. On this basis it is recommended as the treatment of choice for NMGTD.