The molecular mechanisms underlying the genesis and progression of oligodendroglial tumors are poorly understood, since only restricted information on loss of heterozygosity from isolated cases is available. The commonest alterations appear to involve deletion of 1p and 19q, while loss of heterozygosity for 9p, chromosome 10 or epidermal growth factor receptor gene amplification have been described in single tumors. We have applied restriction fragment length polymorphism analysis to 14 loci covering chromosome 1 and 7 loci on chromosome 19 in a series of 25 tumors with an oligodendroglial component to determine precisely the participation of these suppressor genes in the genesis of tumors. Twenty-two and 19 of the 25 samples displayed LOH at 1p and 19q, respectively, and both anomalies were detected in association in 17 samples, including low- and high-grade oligodendrogliomas as well as mixed oligo-astrocytomas. Our findings suggest that inactivation of tumor suppressor genes located on 1p and 19q represent cooperative alterations occurring at early stages of oncogenic transformation of oligodendroglial neoplasms.