Tumor estradiol and progesterone binding sites were studied in 34 patients with meningioma. Twenty of the meningiomas contained very low titers (mean, 45 fmol/g of tumor; range, 0-201 fmol/g of tumor) of a nonspecific cytoplasmic [3H]estradiol binding component, whereas 26 of the tumors contained high titers of specific high-affinity cytosol [3H]promegestone (R5020; progesterone) binding sites (mean, 1476 fmol/g of tumor; range, 0-8328 fmol/g of tumor). No nuclear binding activity for [3H]estradiol could be detected in 12 of the 34 meningiomas studied, irrespective of the progesterone binding activity. There was no correlation between high progesterone binding activity and the age or the sex of the patient, nor between tumor location and cellular mitotic index. However, progesterone binding activity was present more frequently in meningothelial (95%, 18/21 patients) than in transitional (55%, 5/9 patients) or fibroplastic (25%, 1/4 patients) tumor histologic types. These data suggest that the cellular biosynthesis of the progesterone binding component in meningiomas is not estrogen regulated as it is in other classic estrogen target tissues, such as the breast.