Sixty-five patients with high grade central localized osteosarcoma of the extremities were treated according to a neoadjuvant chemotherapy schedule that was comprised of two methotrexate (MTX) cycles (high or moderate dosage) i.v. followed by cisplatinum (CDP) (continuous i.a. infusion for 24 hours). Thirty-four "good" responders (necrosis greater than 90%) were divide in two groups for post-operative treatment. The first group was treated for a short period (4 weeks) with i.v. MTX-CDP; the second group was treated for a longer period (24 weeks) with i.v. MTX-CDP and also adriamycin. Patients in the second group had far better results than the patients in the first group (19/19 vs. 5/15 continuously disease-free patients). Our results following this protocol indicate that even if patients are "good" responders to this neoadjuvant chemotherapy they should not undergo a shortened post-operative treatment, and the protocol should include adriamycin.