The bone density of two groups of patients with osteosarcoma treated with high and low doses of MTX is compared with that of a group of healthy subjects of the same age. Bone density was measured in the radius at the mid point and at the trabecular distal point. In the patients treated with low doses there were differences in bone density as compared with the controls. In those treated with high doses the bone mineral content values were significantly lower than those for the controls (p greater than 0.01) at the trabecular distal point but not at the mid point. The significant reduction in BMC in patients treated with high doses indicated that the osteopaenic effect is dose-dependent. The decrease in density only at the site at which trabecular bone is prevalent shows that MTX acts mainly at the level of this type of bone in accordance with the proven greater sensitivity of trabecular bone to the action of other osteopaenic agents.