The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.