This report evaluates the effect of high-intensity focused ultrasound (HIFU) on subcutaneous murine neuroblastoma C1300. HIFU treatment was administered with a focused 4-MHz quartz transducer with a peak intensity of 550 W/cm2. In experiment 1, 60 animals with tumor were divided into four groups. Group I (n = 15) were controls; group II (n = 15) received adriamycin, 5 mg/kg intraperitoneally; group III (n = 15) received HIFU; and group IV (n = 15) received both adriamycin and HIFU. All the animals in groups I and II died of tumor by 35 days. Fifty-three percent ( 8 15) of mice in group III and 80% ( 12 15) in group IV were cured with no evidence of tumor (NET) at 200 days. Log-rank statistics showed significant prolongation of survival in the groups III and IV as compared with groups I or II (P < .05). In experiment 2, 45 animals with tumor were divided into three groups. Group I (n = 15) were controls; group II (n = 15) received HIFU; and group III (n = 15) received repeated HIFU. The results showed 47% ( 7 15) of mice in group II and 67% ( 10 15) in group III were NET at 200 days. Significant survival prolongation was achieved in groups II and III in comparison with group I (P < .05). In experiment 3, 90 mice received either tumor (n = 60) or saline (n = 30) inoculation in the left flank. On day 5, 45 mice with tumor were treated with HIFU (group I), while the other 15 mice with tumor (group II) had a sham procedure. Nineteen mice in group I were cured with NET (group IA) and 26 had persistent tumor (group IB). The 30 mice receiving saline (without tumor) were treated with either HIFU (group III, n = 15) or a sham procedure (group IV, n = 15). On day 26, all the animals received a second tumor challenge in the right flank. Reduced tumor growth following a second tumor challenge was demonstrated in group IA as compared with other groups (P < .001), implying a stimulation of host tumor immunity following curative HIFU treatment. The data suggest that HIFU may be an alternative modality for the treatment of unresectable neuroblastoma. © 1992.