To determine whether glial growth factor (GGF)-like activity is associated with human Schwann cell tumors, we tested extracts from these tumors for their ability to stimulate the proliferation of rat Schwann cells in culture. Extracts from 3 of 3 bilateral acoustic neuromas and from 5 of 7 unilateral acoustic neuromas demonstrated dose-dependent stimulation similar to that of partially purified bovine pituitary GGF. One neurofibroma also contained high levels of GGF-like activity, one demonstrated an intermediate level, and three showed low or no activity. Minimal activity was found in one neurofibrosarcoma and in one trigeminal schwannoma. Non-Schwann cell tumors studied included 3 meningiomas, 2 pituitary adenomas, 1 cerebellar astrocytoma, 1 glioblastoma, 1 hemangioblastoma, and 2 metastatic brain tumors. The cerebellar hemangioblastoma demonstrated high GGF-like activity; the others showed little or no activity. Normal tissues used as control specimens included brain, peripheral nerve, muscle, and fat. Some activity was noted in one nerve biopsy; all others showed minimal or no GGF-like activity. High-performance liquid chromatography demonstrated that the GGF-like activity from two acoustic neuromas eluted in a single peak close to that of bovine pituitary GGF. We conclude that acoustic neuromas contain a factor that is closely related to bovine pituitary GGF and that this factor may have a role in the abnormal proliferation of Schwann cells in these tumors.