It has long been debated whether the accumulation of allelic losses in tumors involves the selection of cells which have stochastically lost chromosomal regions or whether there is, inherent to the neoplastic state, a process which predisposes to genetic instability. Changes in DNA methylation are commonly seen in human tumors and can alter chromosome structure. We now have examined specific types of primary neural tumors which allow us to determine relationships between abnormal DNA hypermethylation and allelic loss. In primary brain tumors which frequently lose chromosome 17p (30-50%) even in the earliest stages, we now show that 84% (21 of 25) exhibit hypermethylation at locus D17S5, on 17p. However, in primary neuroblastomas, a tumor type which does not lose chromosome 17p, no regional hypermethylation is observed. These data suggest that on chromosome 17p, regional D17S5 hypermethylation constitutes a molecular change which is associated with genetic instability.