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The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is an important step in the control of cell proliferation and development. In particular, IGF-1 and IGF-2 are key regulators of central nervous system development and may modulate the growth of glial tumors. We have investigated the growth factor regulation of the human glioblastoma cell line, T98G. These cells growth arrest in serum-free medium at 34$\sp\circ$C, despite their secretion of substantial amounts of bioactive IGF-1. To be stimulated to divide, growth-arrested cells required the addition of PDGF or its equivalent, 1% serum. Cell proliferation in serum-free medium could also be obtained by shifting the cells to a temperature of 39.6$\sp\circ$C. Treatment of growth-arrested cells with PDGF or a temperature shift was accompanied by a transient increase in the expression of the mRNA for the IGF-1 receptor. Transfection with a plasmid constitutively expressing the full cDNA for the human IGF-1 receptor allowed autonomous growth in serum-free medium at 34$\sp\circ$C. Overexpression of the IGF-1 receptor also led to anchorage-independent growth in these cells. By contrast, growth induction by growth factors or by temperature shift was abrogated by transfection of the cells with a plasmid expressing a 309 bp segment of mRNA anti-sense to the IGF-1 receptor mRNA. Growth in soft agar was also inhibited by expression of anti-sense IGF-1 receptor mRNA. These results demonstrate that the IGF-1 receptor is strictly required for the growth of T98G glioblastoma cells. Moreover, the autocrine interaction of IGF-1 with its receptor regulated the autonomous and anchorage-independent growth of these cells.