N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (LY186641), a novel anticancer compound, was evaluated against six lines of rhabdomyosarcoma xenografts, each of which was established from tissue biopsies from untreated patients, and additional sublines selected as xenografts for primary resistance to vincristine, melphalan, and ifosfamide. LY186641 was given by oral gavage twice daily for 10 consecutive days or as 5-day courses repeated at 7-day intervals. At the optimal schedule, complete regressions of advanced tumors were obtained in each of the six rhabdomyosarcoma lines. There was no apparent cross-resistance in RMS lines selected for vincristine resistance or against multiple-drug-resistance KB cells in vitro. There was slight cross-resistance in xenografts selected for melphalan resistance, but not in an ifosfamide-resistant line. These results indicate that LY186641 may have significant clinical activity in the treatment of childhood rhabdomyosarcoma.