The effects of methotrexate and doxorubicin (Adriamycin) on intact and fractured bone were studied in a rat model. Methotrexate, 0.1 mg/kg i.p., was administered five times a week, or doxorubicin, 1 mg/kg i.v., was given once a week. Animals were killed and evaluated at 4, 8, 12, and 16 weeks after surgical production of a unilateral femoral osteotomy and initiation of the chemotherapeutic program. Both intact and fractured bones were tested to failure in rapid torsion, and the torque, angular deformation, stiffness, and energy were measured. There was a significant alteration in the strength of the healing osteotomies in doxorubicin- and methotrexate-treated animals compared with the control group. The torsional strength of intact bone was not significantly altered by either drug protocol over the period of this observation.