Characteristics of endothelin receptors were studied in male Fischer 344 rats at 4-, 15- and 24-months of age and [ 125I]ET-1 binding showed a single high affinity binding site in their cerebral cortex and spinal cord membranes. The density and affinity of ET binding sites were found to be similar in rats of various age groups. To determine the affinity of ET isotypes to ET-1 binding sites in cerebral cortex and spinal cord, competition studies were performed and K i values of ET-1, ET-2 and ET-3 for [ 125I]ET-1 binding sites were determined. It was found that ET-1 had 100 and ET-2 had 25–100 times lower K i values as compared to ET-3, indicating that ET receptors in cerebral cortex and spinal cord are of ET A type. In spinal cord, the K i values of ET-1 and ET-2 for ET receptor were found to be similar. However, in cerebral cortex the K i values of ET-1 were found to be at least 6 times lower than ET-2. It is inferred that there are two subtypes of ET A receptors, ET A1, which have higher affinity for ET-1 in comparison to ET-2, as found in cerebral cortex and ET A2 which have higher affinity for ET-2, as found in spinal cord. The K i and IC 50 values of ET-1, ET-2, and ET-3 for [ 125I]ET-1 binding sites in cerebral cortex and spinal cord were found to be similar in 4-, 15- and 24-month-old rats. [ 125I]SRT 6b, another ligand which binds to ET receptors, showed that the K i and IC 50 values of ET-1 and ET-2 for [ 125I]SRT 6b binding sites in cerebral cortex and spinal cord were similar in rats of different age groups. K i and IC 50 values of ET-3 for [ 125I]SRT 6b binding sites in cerebral cortex were found to be similar in rats of various age groups. However, the K i and IC 50 values of ET-3 for [ 125I] SRT 6b binding sites in spinal cord of 24-month-old rats were found to be significantly lower as compared to 4- and 15-month-old rats. It is concluded that in cerebral cortex and spinal cord of Fischer 344 rats, ET receptors are of ET A type and there are two subtypes of ET A receptors: ET A1 which have higher affinity for ET-1 as compared to ET-2, as found in cerebral cortex, and ET A2 which have higher affinity for ET-2, as found in spinal cord. The affinity and density of ET receptors in cerebral cortex and spinal cord is similar in rats 4-, 15- and 24-months of age. However, in the spinal cord of 24-month-old rats, the affinity of ET-3 to ET receptors increases significantly as compared to younger rats. The increased sensitivity of spinal cord ET receptors to ET-3 has been attributed to hypertension and the present data indicates a possible mechanism involved in the increase in blood pressure during aging.