The p16 (MTS-1) gene, a candidate tumor suppressor gene, was examined by means of Southern blot, PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) and nucleotide analyses in 5 cases of primary malignant lymphoma of the brain. By Southern blot analysis, the p16 gene was found to be deleted in at least 4 cases, homozygously (3 cases) or hemizygously (1 case). The p15 (MTS-2) gene, another candidate tumor suppressor gene located in the vicinity of the p16 gene, to which it shows structural and functional similarity, was also found to be deleted in 4 cases. Our frequent detection (80%) of p16 and p15 gene deletions might suggest that these deletions are closely related to carcinogenesis in primary malignant lymphoma of the brain. SSCP and nucleotide analyses revealed no mutations of the p16 gene in any of the cases.