The sites in which rhabdomyosarcoma occurs most frequently in children and young adults are the head and neck, genitourinary tract, and the extremities. Among these three sites, tumors of the extremities have been associated with the highest relapse rate and lowest survival rate in patients treated by protocols of the Intergroup Rhabdomyosarcoma Study (IRS). In five of six patients treated by primary extremity amputation, tumor recurred. Seven of 21 patients in Clinical Group I (completely resected tumors), and 9 of 27 patients in Clinical Group II (patients with gross tumor excision but positive lymph nodes, "microscopic residual" disease, or extension beyond the muscle of origin) had relapse. Thirteen of 18 patients (72%) in Clinical Group III (gross residual disease) responded to a chemotherapy-radiotherapy regimen, but ten have subsequently had relapses; and 13 of 18 are dead. Of 30 patients in Clinical Group IV (disseminated disease on entry), 15 initially responded to chemotherapy, but 25 of 30 are dead. The period of surveillance is 2 1/2 to 7 1/2 years, with a mean of 46.3 months at least examination. Increased rates of relapse were seen in patients with extremity tumors, as opposed to tumors in other sites, irrespective of the specific IRS chemotherapy-radiotherapy regimen employed. In Clinical Group I (nonamputation), relapse rates by histologic subtype of rhabdomyosarcoma were alveolar subtype, 5/8; embryonal, 1/7; and all other subtypes, 1/6. Clinical Group II, relapse rates were alveolar, 6/12; embryonal, 5/11; all other subtypes, 3/10.