Lack of DNA-dependent protein kinase (DNA-PK) activity confers radiosensitivity and defective DNA double-strand break repair. Nine human malignant glioma cell lines were studied to determine whether differences in DNA-PK activity reflect differences in inherent radiosensitivity or are predictive of tumor treatment response. DNA-PK activity was present in all cell extracts, as were the DNA-PK proteins, DNA-PK catalytic subunit, Ku p70, and Ku p80. No correlation was found between the levels of DNA-PK activity and inherent radiosensitivity or in the tumor treatment response. These preliminary results suggest that variation in DNA-PK activity may not be a determinant of clinical response in malignant glioma.