This review provides a framework for the neurosurgeon in understanding the increasingly important role of genetics in the study of nervous system tumors. The three tumors discussed (retinoblastoma, meningioma, and neurofibroma) are neither the most common nor the most clinically devastating tumors faced by neurosurgeons. Rather, the studies on these tumors are presented because of the important lessons each provides. Studies of retinoblastoma demonstrate the ability of a gene which is recessive at the cellular level to require a second mutation for tumorigenesis and therein to appear as a dominantly inherited disorder at the level of the organism. This "multi-hit" theory could easily be applied to other nervous system tumors which have both sporadic solitary tumors and familial multiple tumors. In this group we should include acoustic neuromas, meningiomas, gliomas, neurofibromas, paragangliomas (glomus and carotid body tumors), and the pituitary tumors (and others) associated with the multiple endocrine neoplasia syndromes. The limits of this review do not allow a separate discussion of the neurosurgical aspect of these lesions; for this, the reader is referred elsewhere (18, 19). Meningiomas are discussed because it appears that two separate lines of inquiry may eventually be related at a cellular level. These directions of study are the demonstration that a common karyotypic abnormality (monosomy 22) is associated with a female preponderance of meningiomas and the demonstration of sex hormone binding in meningiomas. Future studies should be aimed at showing an in vitro biologic response of these tumors to exogenously added hormones or to their blocking agents. Moreover, one would hope that this response would correlate with a specific chromosomal abnormality. It is possible that some portion of the DNA which has been deleted or altered in these tumors plays an essential role in the regulation of the sex steroid regulatory system. If this segment of the genome could be identified and studied in the meningioma, the findings could be important not only in the treatment of patients with this tumor but also in the treatment of tumors of other hormonally modulated tissues such as breast and uterus. Finally, neurofibromatosis was chosen as the most common of the phakomatoses and as one which can offer significant insights into many areas of neuro-oncology. The NF gene occurs in at least two forms (VRNF, BANF), and it can be associated with virtually all of the tumors known to neurosurgeons--gliomas, neurofibromas, schwannomas, and meningiomas.(ABSTRACT TRUNCATED AT 400 WORDS)