The HindIII c-sis RFLP was analyzed in constitutional and tumor DNAs of 19 meningioma patients. Loss of a c-sis allele (allele I in all cases) was observed in 6 out of 10 tumors from heterozygous patients. No alteration in the structure or dosage of the c-sis gene was detected in any tumor sample. Northern analysis of c-sis evidenced sis transcripts in 7 out of 8 meningiomas which were amenable to analysis. All tumors expressing c-sis also expressed c-fos, suggesting that the autocrine loop elicited by sis activation may have c-fos as its nuclear target. Co-expression of c-sis and c-fos was also observed in 5 neuromas out of 7 analyzed. Very high levels of fos-mRNA were observed in 2 neuromas, but were not found to be caused by apparent alteration or amplification of the c-fos gene.