Accumulated clinical evidence suggests that alveolar rhabdomyosarcoma (ARMS) is more aggressive than embryonal rhabdomyosarcoma (ERMS). Here, we study six childhood rhabdomyosarcoma cell lines, three ERMS and three ARMS. We have assayed the ability of the tumor cells to grow in culture and in nude mice as well as their propensity for pulmonary metastasis formation by tail vein injection. We also compared levels of c- and N-myc oncogene expression and DNA copy number. We find no correlation of histologic tumor type (i.e. ERMS versus ARMS) with growth rate in culture, but we do find suggestive correlations of histologic type with tumorigenicity (mean tumor diameter in millimeters at 6 wk: ARMS 30, ERMS 10; p1 = 0.1) and metastasis formation (ARMS 12, ERMS 0; p1 = 0.1). These properties also correlate with uniform greater overexpression of c-myc in ARMS (mean 39.3-fold, range 16-83) compared with ERMS (mean 5.3, range 4-8) (p1 = 0.05, control fibroblasts = 1). Although c-myc was often amplified in vitro (four of six lines), there was no correlation with histologic type (2/3 ARMS, 2/3 ERMS). These data on rhabdomyosarcoma cell lines derived from verified ERMS and ARMS tumors support the impression from previous clinicopathologic observations that ARMS is a more malignant form of rhabdomyosarcoma than ERMS.