We have characterized the endothelin (ET) receptor subtypes present within normal human cerebral cortex (CC), glioblastoma multiforme (GBM), and meningiomas (MGs), using two subtype-selective radioligands, [125I]-PD151242 (ETA) and [125I]-BQ3020 (ETB). For saturation experiments, sections of tissue were incubated with increasing concentrations (8 pM-4 nM) of either [125I]-PD151242 or [125I]-BQ3020 in incubation buffer (22 degrees C, 2 h). In saturation binding assays, [125I]-PD151242 bound with high affinity to a single population of ET receptors (n = individuals; +/- SEM) in normal CC (n = 3; Kd 1.23 +/- 0.20 nM; Bmax 28.10 +/- 9.04 fmol/mg protein), GBM (n = 5; Kd 1.62 +/- 0.20 nM; Bmax 147.04 +/- 62.8 fmol/mg protein), and MGs (n = 3; Kd 3.10 +/- 0.44 nM; Bmax 290.3 +/- 105.8 fmol/mg protein). [125I]-BQ3020 also bound with high affinity to a single population of ET receptors in normal CC (n = 3; Kd 4.54 +/- 1.58 nM; Bmax 190.5 +/- 88.8 fmol/mg protein), GBM (n = 4; Kd 1.38 +/- 0.28 nM; Bmax 234.0 +/- 153.6 fmol/mg protein), and MGs (n = 3; Kd 0.25 +/- 0.09 nM; Bmax 22.8 +/- 18.0 fmol/mg protein). To determine receptor subtype localization, autoradiography was performed after incubation of sections with 0.1 nM [125I]-ET-1 (ETA and ETB), [125I]-PD151242 (ETA), and [125I]-BQ3020 (ETB). Autoradiography demonstrated a high concentration of ETA receptors within the pial and intraparenchymal vessels and meninges overlying the CC. Gray and white matter were diffusely ETB-positive. GBM had a strongly vascular pattern of ETA distribution. ETA receptors were dense and homogeneous in MGs. [125I]-PD151242 binds with high affinity to human pial and intraparenchymal vessels and is able to clearly delineate the microvasculature in GBM. Selective ETA receptor manipulation may have potential benefits in cerebrovascular disease and neoplasia without producing detrimental effects on the predominantly ETB-positive brain parenchyma.