To evaluate the expression of transforming growth factor-alpha(TGF-alpha) and proliferating cell nuclear antigen(PCNA) and its relation to the differentiation of the tumors, immunohistochemical studies were performed in 49 human gliomas. Tumors were graded by a 3-grade-system; grade I=low grade glioma, grade Il=anaplastic glioma, grade III=glioblastoma multiforme. TGF-A and PCNA were predominantly expressed in malignant gliomas compared with benign gliomas. Malignant gliomas revealed 87% TGF-A reactivity, while benign gliomas revealed 26% TGF-A reactivity. The proliferation index with PCNA was 26%+/-7%(mean+/-standard deviation) in malignant gliomas and 5%?% in benign gliomas. A strong positive correlation between tumor grade and extent of TGF-A and PCNA expression was found(P<0.0001, Chi square and P<0.002, T-test). Synchronous expression of TGF-A and PCNA was observed in 16 cases(33%). The results of this study support the suggestion that the expression of TGF-A might be a useful prognostic indicator in human gliomas.