Several established human glioma cell lines have been previously shown to express the common acute lymphoblastic leukemia antigen (cALLa, CD 10), an important marker in the diagnosis of human acute lymphocytic leukemia (ALL). The amino acid sequence of cALLa is identical to that of neutral endopeptidase (NEP,E.C.3.4.24.11), and cALLa expressed on leukemia and melanoma cell lines is enzymatically active NEP. In the present study, we investigated whether cALLa expressed on glioma cell lines is active NEP. We detected cALLa on 10 out of 13 glioma cell lines using 2 different anti-cALLa MAbs (A12-G4 and FAH99). NEP antigen, as detected by immunostaining with an anti-NEP MAb (135A3), was expressed on the same 10 lines. cALLa-positive, but not cALLa-negative cell lines displayed an endopeptidase activity. This activity could be blocked by phosphoramidon, a specific inhibitor of NEP. Furthermore, mRNAs hybridizing to an NEP-specific probe were present in cALLa-positive glioma cells but not in cALLa-negative cells. Taken together, the results provide strong evidence that cALLa-positive glioma cell lines express endopeptidase activity on the cell surface.