570 patients with osteosarcoma of the extremities were treated with five different protocols of neoadjuvant chemotherapy at Rizzoli Institute between 1983 and 1995. Surgery consisted of limb salvage in 83% rotation plasty in 5% and amputation in 12%. The 5-year event-free survival (EFS) was 60% which varied according to the protocol followed, ranging from 47.6% to 66.4%. 234 patients relapsed. The pattern of relapse was analysed. The mean relapse time was 23.8 months (range: 2-96). The first site of systemic relapse was the lung in 88% (32% of these had less than three pulmonary metastases and 68% three or more), bone in 9%, lung and bone in 2% and other sites in 3%. The relapse time and the number of pulmonary metastases were strictly correlated with the efficacy of the protocol of chemotherapy used. Patients treated with the three protocols that gave a 5-year EFS of more than 60% relapsed later and had fewer pulmonary lesions than patients treated with the two protocols that gave a 5-year EFS of 47.6% and 52.5%. The rate of local recurrence was relatively low (6%). This was not correlated with the protocol or the type of surgery used: limb salvage (6.4%), rotation plasty or amputation (4.1%). However, the rate of local recurrence was very high (21.9%) in the few patients (7%) that had less than wide surgical margins. We conclude that for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy: (a) the pattern of systemic relapse changes according to the efficacy of the protocol of chemotherapy used. This should be always considered when evaluating the preliminary results of new studies as well as in defining the time of follow-up; (b) limb salvage procedures are safe and do not jeopardise the outcome of the patient, provided that wide surgical margins are achieved.