Long-term disease-free survival is poor in patients with primary generalized or relapsed solid tumors. High-dose chemoradiotherapy with stem cell rescue improved survival, but more effective protocols are needed. From January 1988 to November 1988, we treated 7 patients (median age, 9 years; range, 3-23 years) with an intensified treatment program. They received 12-Gy fractionated, total-body irradiation (FTBI). High-dose chemotherapy (MEC) consisted of melphalan (120-140 mg/m2 Mel) and etoposide (40-60 mg/kg VP-16) with or without carboplatin (1.5 g/m2 CBDCA). Although we combined 12-Gy FTBI with Mel, VP-16, +/- CBDCA in doses used previously for high-dose single-agent chemotherapy, the extramedullary toxicity of FTBI with ME(C) was tolerable. Two of the four patients who were grafted without delay after good initial chemotherapy response are still alive in continued complete remission 30 and 33 months, respectively, after initial diagnosis. Early application of FTBI and ME(C) during first chemotherapy response might improve outcome in patients with primarily generalized solid tumors.