The objective of this study was to examine the expression of transforming growth factor alpha (TGF alpha), a mitogen for many cell types, and its receptor in basic subtypes of meningiomas as well as in meningiomas of varying grade. Formalin-fixed tissues from 26 meningiomas including 15 benign (5 meningothelial, 5 transitional, and 5 fibrous variants), 6 atypical, and 5 malignant examples were immunohistochemically examined for both TGF alpha protein and EGF/TGF alpha receptor protein. In addition, in situ hybridization (ISH) was used to detect TGF alpha mRNA expression. Immunostaining for TGF alpha was strongest in fibrous and atypical meningiomas, followed closely by transitional and malignant tumors. Only weak reactivity was observed in the meningothelial variant. In all but 4 tumors (2 fibrous, 2 atypical), ISH showed TGF alpha mRNA to be present, the signal being stronger in malignant than in conventional or atypical tumors. Lastly, immunostaining for EGF/TGFa receptor was positive in all tumors studied. Strong TGF alpha protein expression in meningiomas is commonly associated with fibrous morphology. Although the frequent detection of both TGF alpha protein and its mRNA, as well as of EGF/TGF alpha receptor within tumors of all type and grades, suggests that TGF alpha serves to promote tumor growth, its possible role in tumorigenesis or malignant progression is uncertain. In summary, demonstration of these substances is of no utility in the classification or grading of this common tumor because the differences in their expression among the various meningioma subtypes were not statistically significant.