Twenty-seven previously untreated children with gross residual (20) or metastatic (seven) rhabdomyosarcoma were treated with pulse-VAC (vincristine weekly for 12 doses plus dactinomycin and cyclophosphamide simultaneously given daily for 5 days) and radiotherapy. Toxicity during the 12-week induction period included 23 of 27 (85%) with an absolute neutrophil count (ANC) under 500/mm3; 16/27 (59%) were given intravenous (I.V.) antibodies. Three patients developed Gram-negative sepsis and two of them died. In the first 12 weeks, eight children had a complete response (CR) and another 10 a good partial response (PR), a total of 18 of 27 favorable responses (67%). At 12 weeks, 20 patients received either intermittent pulse-VAC (Regimen H) or a pulse of adriamycin plus vincristine and cyclophosphamide alternating with pulse-VAC (Regimen I) every 4--6 weeks. After this first "maintenance," only seven patients (35%) developed an ANC under 500/mm3 and only three (15%) were given I.V. antibiotics. Severe toxicity disappeared with drug dose reduction in subsequent courses. The overall CR rate was 59% with a PR rate of 15%, a total of 74% favorable responses. This rate is not significantly better than that obtained by previous IRS chemotherapy and radiotherapy schedules for patients with gross residual and metastatic rhabdomyosarcoma. Future studies in these patients will concentrate on diminishing myelosuppression while shortening the rest period between pulses, in order to deliver more drug per unit time.