Meningiomas are common tumours derived from the thin membrane that surrounds the brain and spinal cord. Currently, the molecular mechanisms responsible for the initiation and progression of these tumors are largely unknown. Toward the elucidation of such mechanisms, we have formulated an experimental design utilizing the technique of subtractive hybridization that is aimed at identifying the changes in gene expression between intracranial meningiomas and their normal precursor cells, leptomeningeal cells. We report here the identification and initial characterization of three genes whose expression is altered or aberrant in meningioma cell lines and tumours relative to cultures of normal leptomeningeal cells. Complementary DNA probes from one of these genes detect transcripts of altered size in several meningiomas relative to normal leptomeningeal cells. Another of these genes demonstrates decreased expression in meningiomas and in tumours associated with the disorder neurofibromatosis 2. A third gene isolated by this procedure is differentially expressed in both meningiomas and breast carcinomas. Therefore, the decreased expression of these genes may play roles in growth-regulatory pathways that are abrogated not only in meningiomas, but in other tumor types as well.