In 19 human meningiomas (14 primary and four recurrent tumors and one tumor transplanted into athymic nude mice), oncogene expression, amplification, and rearrangement, and loss of heterozygosity on chromosome 22 were examined. Compared to nontumor brain tissue, there was greater than a fivefold expression of the sis oncogene in six (40%) of 15 tumors studied and of the c-myc oncogene in 12 (63%) of the total 19 tumors. Expression of the sis gene was lower in the recurrent tumors than in the primary cases, and there was no detectable expression in anaplastic meningioma cells. Rearrangement of the sis gene was found in one meningioma. Loss of heterozygosity on chromosome 22 was detected in two of the five informative heterozygous cases. Expression of the c-myc gene was higher in cases with a loss of heterozygosity than in those without. These results suggest that the sis and c-myc oncogenes are associated with tumorigenicity and that c-myc may induce meningiomas through loss of the putative tumor suppressor gene.