The effect of local extent of the tumor on disease-free survival was studied in fifty-one patients who had an osteosarcoma, all of whom were treated according to the same protocol. Disease-free survival was defined as the interval between entry into the protocol and local recurrence, metastasis, or death (whichever occurred first). All patients had a Stage-IIB intramedullary osteosarcoma--that is, a high-grade malignant tumor (Stage II) with cortical penetration (B). The tumors were subdivided on the basis of the amount of local extension: E1--the tumor touches but does not elevate or penetrate the periosteum; E2--the tumor elevates but does not penetrate the periosteum; E3--the tumor penetrates into, but not through, the periosteum; E4--there is minimum extraperiosteal extension without invasion of another structure, such as a muscle, tendon, or ligament; E5--the tumor invades one additional structure (a muscle, ligament, or tendon); and E6--the tumor invades two or more structures adjacent to the bone. When the tumor had invaded two or more adjacent structures (E6), the instantaneous risk of failure was estimated to be 5.9 times greater than when the tumor had a lesser extent (E1 through E5). The relative prognostic importance of the amount of local extension, the size of the tumor, and the sex and age of the patient was compared with forward step-wise Cox multivariate analysis. Only the amount of local extension had a significant effect on disease-free survival. The estimated cumulative probabilities of disease-free survival at five years, according to the Kaplan-Meier method, were 49.1 +/- 8.5 per cent for patients who had a Stage-IIB tumor, 79.8 +/- 9.3 per cent for those who had a Stage-IIB but not E6 tumor, and 17.6 +/- 11.3 per cent for those who had a Stage-IIB E6 tumor. These data suggest that, with respect to prognosis, there are two distinct subgroups of Stage-IIB osteosarcomas that can be objectively defined by the amount of local extension.