The gene amplification and expression of transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGF-R) in human gliomas was determined by Southern blot analysis and a receptor binding study. Amplification of the EGF-R gene was demonstrated in 3 of 11 tumors examined. All were glioblastomas, whereas the TGF-alpha gene was amplified in 7 of 11 tumors, and 6 of the 7 were recurrent glioblastomas and anaplastic astrocytomas. A competitive binding study with iodinated EGF showed a TGF-alpha-like activity ranging from 1.6-31.5 ng of EGF/microgram protein. These results suggest a differential expression of EGF-R and TGF-alpha genes among untreated and recurrent malignant gliomas.