Tumor cells are characterized by abnormalities in growth and metabolism, including the autocrine secretion of certain growth factors. The authors have previously shown the presence of insulin-like growth factor receptors in tumors of the central nervous system (CNS) and in this study examine whether CNS tumors are capable of autocrine secretion of insulin-like growth factors in situ. To investigate the production of insulin-like growth factors I and II by CNS tumors, the authors have developed specific radioimmunoassays for these growth factors. In situ production of insulin-like growth factors was studied by immunoassay of CNS tumor cyst fluid aspirated at the time of surgery from 12 cystic tumors: seven primary brain tumors, four metastatic tumors, and one spinal schwannoma. For immunoassay, cyst fluid was treated overnight with acetic acid, then insulin-like growth factors were separated from binding proteins by a refined solid-phase technique, then dried and reconstituted in immunoassay buffer. Normal human serum and cerebrospinal fluid served as controls. Insulin-like growth factor I was detected in all 12 tumors studied. In contrast, insulin-like growth factor II was detected only in three low-grade astrocytomas, the spinal schwannoma (which had the highest insulin-like growth factor II level of all tumors studied), and three metastatic lung cancers. These results suggest that CNS tumors may be capable of autocrine production of insulin-like growth factors in situ. Furthermore, there appears to be a difference in the type of insulin-like growth factors produced by different types of CNS tumors. Preferential production of insulin-like growth factors may be an important marker of tumor differentiation and useful as a diagnostic tool.