Benign meningioma tumors possess significant levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Two different 17β-HSDs were discovered in human placenta: one highly estrogen specific and using NADP-VNADPH as cofactors (type-1 17β-HSD), and a second one that utilizes both androgens and estrogens as substrates with NAD+/NADH (type-2 17β-HSD). Recently, two further human 17β-HSDs were isolated. A testis-specific 17β-HSD (type-3 Πβ-HSD) favors the reduction of △4-androstenedione to testosterone, and a ubiquitously expressed type-4 17β-HSD preferentially catalyzes the oxidation of estradiol and Δ5-androstenediol. In this study we characterize the expression levels of different types of 17β-HSD in a wide series of tumors. Using the Northern blotting method we show that type-1, -3, and -4 17β-HSDs are not detectable in meningiomas. In contrast, the type-2 17β-HSD RNA is present in 6 of 17 meningiomas and its abundance is directly correlated with estrogenic 17β-HSD activity (r2 = 0.74). The presence of type-2 17β-HSD is also demonstrated by in situ hybridization. RT-PCR and Western blots show that type-4 17β-HSD is also present, though at much lower levels. The progesterone receptor level, the epidermal growth factor receptor level, and the age of the patients are not correlated with the estrogenic 17β-HSD activity or type-2 17β-HSD m